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Probiotics and Disease Prevention
CHARLES E HENLEY DO MS MPH FAAFP FACOFP
ASSOCIATE DEAN FOR CLINICAL AFFAIRS MARIAN UNIVERSITY COLLEGE O F OSTEOPATHIC MEDICINE
What are ProbioticsFAOWHO Definition
ldquoLive microorganisms which when administered in adequate amounts confer a health benefit on the hostrdquo
Probiotic microorganisms can be found in both supplement form and as components of foods and beverages
The Joint Food and Agriculture OrganizationWorld Health Organization Working Group
US Specialty Supplement Sales by Product in 2009
Source Nutrition Business Journal estimates (consumer sales)
Based on NMIrsquos Health and Wellness Trends Database
US Health and Wellness Industry
2009 Sales = $1123 Billion
Functional and Fortified Foods and Beverages in 2009 = $405 Billion
Vitamins Minerals Herbals and supplements in 2009 = $233 Billion
Probiotic supplements in 2009 estimated at $405 million
4
17
6191
191
453432
564
307
271
127
421
294
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
(Number of published clinical studies on probiotics)
Polynomial trend line shows uniform consistent growth
Clinical Research Activities Trended
Source wwwncbinlmnihgovpubmed
Role of microbes in the gut
Microbes supply essential nutrients by breaking down complex carbohydrates
They generate secondary bile acids that assist in digesting fats
They synthesize vitamins such as K B12 folate and biotin
Contributes to the defensive barrier in the colon by keeping pathogenic bacteria from crossing the colonic mucosa
Interacts with our systemic immune system in a way that maintains a level of homeostasis allowing for appropriate activation in the face of pathogens without developing autoimmunity
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
What are ProbioticsFAOWHO Definition
ldquoLive microorganisms which when administered in adequate amounts confer a health benefit on the hostrdquo
Probiotic microorganisms can be found in both supplement form and as components of foods and beverages
The Joint Food and Agriculture OrganizationWorld Health Organization Working Group
US Specialty Supplement Sales by Product in 2009
Source Nutrition Business Journal estimates (consumer sales)
Based on NMIrsquos Health and Wellness Trends Database
US Health and Wellness Industry
2009 Sales = $1123 Billion
Functional and Fortified Foods and Beverages in 2009 = $405 Billion
Vitamins Minerals Herbals and supplements in 2009 = $233 Billion
Probiotic supplements in 2009 estimated at $405 million
4
17
6191
191
453432
564
307
271
127
421
294
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
(Number of published clinical studies on probiotics)
Polynomial trend line shows uniform consistent growth
Clinical Research Activities Trended
Source wwwncbinlmnihgovpubmed
Role of microbes in the gut
Microbes supply essential nutrients by breaking down complex carbohydrates
They generate secondary bile acids that assist in digesting fats
They synthesize vitamins such as K B12 folate and biotin
Contributes to the defensive barrier in the colon by keeping pathogenic bacteria from crossing the colonic mucosa
Interacts with our systemic immune system in a way that maintains a level of homeostasis allowing for appropriate activation in the face of pathogens without developing autoimmunity
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
US Specialty Supplement Sales by Product in 2009
Source Nutrition Business Journal estimates (consumer sales)
Based on NMIrsquos Health and Wellness Trends Database
US Health and Wellness Industry
2009 Sales = $1123 Billion
Functional and Fortified Foods and Beverages in 2009 = $405 Billion
Vitamins Minerals Herbals and supplements in 2009 = $233 Billion
Probiotic supplements in 2009 estimated at $405 million
4
17
6191
191
453432
564
307
271
127
421
294
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
(Number of published clinical studies on probiotics)
Polynomial trend line shows uniform consistent growth
Clinical Research Activities Trended
Source wwwncbinlmnihgovpubmed
Role of microbes in the gut
Microbes supply essential nutrients by breaking down complex carbohydrates
They generate secondary bile acids that assist in digesting fats
They synthesize vitamins such as K B12 folate and biotin
Contributes to the defensive barrier in the colon by keeping pathogenic bacteria from crossing the colonic mucosa
Interacts with our systemic immune system in a way that maintains a level of homeostasis allowing for appropriate activation in the face of pathogens without developing autoimmunity
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
4
17
6191
191
453432
564
307
271
127
421
294
19
97
19
98
19
99
20
00
20
01
20
02
20
03
20
04
20
05
20
06
20
07
20
08
(Number of published clinical studies on probiotics)
Polynomial trend line shows uniform consistent growth
Clinical Research Activities Trended
Source wwwncbinlmnihgovpubmed
Role of microbes in the gut
Microbes supply essential nutrients by breaking down complex carbohydrates
They generate secondary bile acids that assist in digesting fats
They synthesize vitamins such as K B12 folate and biotin
Contributes to the defensive barrier in the colon by keeping pathogenic bacteria from crossing the colonic mucosa
Interacts with our systemic immune system in a way that maintains a level of homeostasis allowing for appropriate activation in the face of pathogens without developing autoimmunity
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Role of microbes in the gut
Microbes supply essential nutrients by breaking down complex carbohydrates
They generate secondary bile acids that assist in digesting fats
They synthesize vitamins such as K B12 folate and biotin
Contributes to the defensive barrier in the colon by keeping pathogenic bacteria from crossing the colonic mucosa
Interacts with our systemic immune system in a way that maintains a level of homeostasis allowing for appropriate activation in the face of pathogens without developing autoimmunity
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Gut ColonizationColonization of the gastrointestinal tract begins immediately after birth
Colonization pattern is affected by mode and type of birth delivery
initial diet
geographical location
Initial bacterial colonization (normal) starts from a ldquoGerm freerdquo intrauterine environment and is populated through maternal vaginalfecal flora and oral feeding (breast milk vs formula)
Complete adult colonization 18 ndash 24 months
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Functions of the Intestinal Flora
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Gut-brain axis
Gut flora plays a role in communication between the central nervous
system and the enteric nervous system
Modulates hormonal and neural pathways
Associated with such diseases as irritable bowel syndrome (IBS) and certain psychiatric disorders
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Decreased Microbial diversity
May be at the heart of many gut problems A decrease in microbial diversity is associated with elevation of certain disease markers for things like insulin triglycerides C-reactive protein and obesity
Soluble fiber adds to the greatest long term improvement in microbial diversity
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Gut functionAcute diarrheaAAD travelers diarrheaC difficileLactose digestionIBS symptomsColicInflammatory bowel
conditionsGut pain sensation
AllergyAtopic dermatitisAsthma
Oral microbiologyDental caries
Colds respiratory infections
Skin microbiology inflammation
Vaginal infections
Metabolic syndromeObesity Diabetes
Encompassing effectsbullGrowth parameters of undernourished childrenbullReduced absences from work daycarebullQOL
Diverse Targets for Probiotics
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Evidence for use in digestive disorders Irritable bowel disease (IBS)
Altered intestinal transit
Low grade colonic inflammation
Alterations in gut-brain axis
A meta-analysis of 43 randomized controlled trials found probiotics to decrease global IBS symptoms abdominal pain and bloating (Lactobacillus and Bifidobacterium)
Soluble fiber improves the effect even more
The IOMrsquos daily recommended intake of soluble fiber is 15 gd
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Inflammatory bowel disease (IBD)
Inflammation of the gut caused by an overactive immune response
Altered microbial composition an increase in bacteria that produce pro-inflammatory cytokines and a decrease in bacteria that have a dampening effect on immune system activation
There are studies where combinations of probiotics that can both induce and maintain remission in patients with ulceration colitis but not for patients with Crohnrsquos disease
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Diarrheal illness
Healthy bacteria normally block the actions of pathogenic bacteria and protect against diarrheal illness (Colonization resistance)
1 Probiotics can prevent several types of diarrheal illness such as antibioticassociated diarrhea (AAD)
2 Acute infectious diarrhea and travelerrsquos diarrhea (TD)
A meta-analysis of 12 studies showed that Probiotics could prevent up to 85
of cases of TD
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Antibiotic Associated Diarrhea (ADD)More than a third of patients taking antibiotics develop AAD and in 17 of cases AAD is fatal
Although Current evidence leads to uncertainty whether mild CDAD needs to be treated
Antibiotic treatment may disturb the resistance of gastrointestinal flora to colonization This may result in complications the most serious of which is Clostridium difficilendashassociated diarrhea (CDAD)
Pseudomembranous colitis secondary to C difficile is the main cause of AAD-related mortality
AAD is associated with several pathogens including Clostridium difficile Clostridium perfringens Klebsiella oxytoca and Staphylococcus aureus
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
ADD StudiesHempel et al reviewed 82 studies and pooled data from 63 RCTs (N=11811) to identify the relative risk (RR) of AAD among patients who received probiotics during antibiotic treatment compared with those who received no probiotics or were given a placebo1
The pooled RR for AAD in the probiotics groups was 058 (95 confidence interval 050-068 Plt001) with a number needed to treat of 13
Probiotics appear to be effective in preventing and treating AAD in children and adults receiving a wide variety of antibiotics for a number of conditions
a reduction of 66 in C difficile-associated diarrhea in patients taking probiotics with their antibiotics
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Metabolic Disorders
The gut bacteria can affect energy metabolism
In obesity there is decreased production of short chain fatty acids by bacteria leading to a pro-inflammatory state
Probiotics containing Bifidobacterium and lactobacillus can help correct this by increasing production of short chain free fatty acids
There is no evidence to support supplementing with probiotics to lose weight
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Diabetes
Studies have found that probiotics have beneficial effects on glycemic control especially in animal studies
A systemic review of 33 studies of probiotic use in diabetes including 5 clinical trials found a significant reduction in at least one of six parameters of glucose control fasting plasma glucose post prandial blood glucose glycated hemoglobin insulin and insulin resistance as well as the onset of diabetes
It is not clear which strains of probiotic confer the benefit
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Psychiatric Illness
The gut-brain axis is thought to also impact mental health
It may theoretically impact the hypothalamic-pituitary-adrenal axis activate the immune system producing active metabolites and cytokines and affect the vagus nerve There are no studies to definitively demonstrate this but there have been studies on depression and autism spectrum disorder where there has been a benefit
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Depression
Comparison between depressed patients and healthy controls have demonstrated differences in in patterns of over and under represented microbial species in in depressed patients
Some studies have shown that patients who used probiotics did better on depression scores
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Probiotics could someday treat depression and anxiety
Mice who drank a broth spiked with the organism Lactobacillus rhamnosus (JB-1) produced less of the stress hormone corticosterone in their brains in response to a stressful event
Researchers believe the vagus nerve plays a key role in allowing bacteria in the gut to influence the brain In their experiments L rhamnosus (JB-1) was helpful only in mice with an intact vagusnerve not in mice who had a portion of the nerve removed
It appears that the gut bacteria helped normalize the expression of important neurotransmitters in the brain that would naturally be turned up or turned down when animals become stressed or anxious
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Autism Spectrum Disorder (ASD)
Clinically children with ASD have more complaints of GI problems such as diarrheaconstipation and bloating than do healthy controls
This association leads us to consider a possible connection with the gut-brain axis Several studies have found an increase in Clostridium Species in ASD
Information on using probiotics to treat ASD is non existent in the present literature
Small studies using dietary modifications such as gluten free and casein free diets have been inconclusive
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Rheumatoid arthritis (RA)
The exact influence of gut flora on RA is unknown but there is a T-helper cell function in the pathogenesis of RA and in patients with the disease and changes in the gut flora can effect the balance of the T-helper subsets One study of RA patients showed that 75 of those patients with new onset RA had a predominant gut flora of Pre-votella Copri bacteria and patients with a chronic form of RA had a decrease in bacteroides species compared with healthy controls
Data on using probiotics to alleviate symptoms of RA is mixed
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Eczema
Several studies have looked at the relationship between probiotic use and the risk for allergic illness
A recent Cochrane review found strong evidence that probiotics can prevent eczema (atopic dermatitis) in high-risk infants under the age of two Although they may be able to prevent eczema they appear to be ineffective in treating other allergic illnesses
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
The SOR system for ranking evidence
Level A Good-quality patient-oriented evidence (double blinded clinical trials)
Level B Inconsistent or limited-quality patient-oriented evidence
Level C Consensus usual practice opinion disease-oriented evidence case series
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases
Condition The Evidence Recommendedtreatment
Level of evidence
Irritable bowel syndrome Probiotics significantlydecrease global IBS symptoms abdominal pain bloating and flatulence
A mixture of Lactobacillus and Bifidobacterium species approximately 20-40 billion CFUd for 4-6 weeks
A
Inflammatory bowel disease
Probiotics induce and maintain remission in ulcerative colitis no beneficial effects for Crohnrsquos disease
A mixture of Lactobacillus and Bifidobacterium species 225 billion CFUd for 8-12 weeks to induce remission or longer to maintain remission
A
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Condition The Evidence Recommendedtreatment
Level of evidence
Antibiotic-associated diarrhea
Probiotics reduce risk of developing AAD
Lactobacillus alone or in combination with Bifidobacterium species 10-20 billion CFUd for 7 days or Saccharomyces boulardii 250-500 mg (5-10 billion CFU) twice a day for 2 weeks
A
Acute infectious diarrhea
Probiotics shorten duration and reduce severity of illiness
L casei rhamnosus GG 10-20billion CFUd for 5-7 days or Saccharomyces boulardii500 mgd for 5-7 days
B
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Condition The evidence Recommended treatment Level of evidence
Travelers diarrhea Probiotics prevent up to 85 of cases of travelers diarrhea
Saccharomyces boulardii500mgd for 3 weeks or Lactobacillus alone or in combination with Bifidobacterium 20 billion CFUd for 3 weeks
B
Eczema Probiotics may prevent eczema in the first 2 years of life
Galacto- and fructo-oligosaccharide (91 ratio) (68gL) and acidic oligosaccharide (12 gl) in infants OR Galacto- and fructo-oligosaccharide (GOSFOS 91 ratio) (8 gL) in infants
B
Diabetes Probiotics result in significant reduction in at least one of 6 parameters of glycemic control
Lactobacillus alone or in combination withBifidobacterium 10-40 billion CFUd for 6-8 weeks
C
Probiotics and prebiotics Which of your patients might benefitThe following table summarizes the evidence for using probiotics for specific diseases Continued (Inserted from The Journal Of Family Practice Vol 65 NO 1)
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Probiotic strain Recommended daily dosage Preparations
Lactobacillus rhamnosus GG 10 billion CFUs Capsules (Culturelle)
Therapeutic yogurts and fermented milks
Lactobacillus spBifidobacterium spdagger
100 million to 35 billion CFUs depending on preparation
Capsules (Align Primadophilus)
Powder (Primal Defense)
Capsules or powder (Fem-Dophilus Jarro-Dophilus)
Therapeutic yogurts and fermented milks (Activia Danactive Yo-Plus)
Saccharomyces boulardii 250 mg to 500 mg Capsules (Florastor)
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Different types of microbes used as probiotics
Lactobacillus
Bifidobacterium
S thermophilus
Saccharomyces
Propionibacterium
Bacillus
Enterococcus
E coli
Images courtesy of Prof Lorenzo Morelli
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Not Allowable ClaimsThe FDA does not allow any statements on a food or supplement that would communicate benefits on
Reducing the risk of acute diseases (colds flu GI infections)
Managing symptoms in people who are not healthy (in-patients or people with a diagnosed condition such as IBS)
Improving therapeutic efficacy of a drug
Managing side effects of a drug (eg antibiotics)(Even if such use is recognized as safe in the target populations)
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Regardless of the claim it must be substantiated
There are no generic probiotic claims
Claim substantiation must be based on a specific strain
Probiotic claims
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
PRACTICE RECOMMENDATIONSHowever some recommendations can be made
rsaquo Encourage patients to eat a healthy diet that includes an adequate amount of soluble fiber to maintain a healthy diverse microbiome B
rsaquo Recommend combination probiotics to treat symptoms of irritable bowel syndrome A
rsaquo Recommend that patients taking antibiotics also take probiotics containing Lactobacillus species to prevent antibiotic-associated diarrhea and Saccharomyces to prevent Clostridium difficileinfection A
rsaquo Recommend probiotics containing Lactobacillus species andor Saccharomyces to treat acute infectious diarrhea A
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Selected Bibliography1 Hempel S Newberry S Maher A et al Probiotics for the prevention and treatment of antibiotic-associated diarrhea JAMA 2012307 1959-1969
2 Johnston BC1 Ma SS Goldenberg JZ Thorlund K Vandvik PO Loeb M Guyatt GH Probiotics for the prevention of Clostridium difficile-associated diarrhea a systematic review and meta-analysis Ann Intern Med 2012 Dec 18157(12)878-88
3 Johnston BC1 Goldenberg JZ Vandvik PO Sun X Guyatt GH Probiotics for the prevention of pediatric antibiotic-associated diarrhea Cochrane Database Syst Rev 2011 Nov 9(11)CD004827 doi 10100214651858CD004827pub3
4 Goldenberg JZ1 Ma SS Saxton JD Martzen MR Vandvik PO Thorlund K Guyatt GH Johnston BC Probiotics for the prevention of Clostridium difficile-associated diarrhea in adults and children Cochrane Database Syst Rev 2013 May 315CD006095 doi 10100214651858CD006095pub3
5 Nelson RL1 Kelsey P Leeman H Meardon N Patel H Paul K Rees R Taylor B Wood E Malakun R Antibiotic treatment for Clostridium difficile-associated diarrhea in adults Cochrane Database Syst Rev 2011 Sep 7(9)CD004610 doi 10100214651858CD004610pub4
6 Blake Rodgers MDcorresponding author Kate Kirley MD and Anne Mounsey MD Prescribing an antibiotic Pair it with probiotics J Fam Pract 2013 Mar 62(3) 148ndash150
7 Prescott SL Dunstan JA Hale J et al Clinical effects of probiotics are associated with increased interferon-gamma responses in very young children with atopic dermatitis Clin Exp Allergy 200535(12)1557ndash1564
8 Rosenfeldt V Benfeldt E Valerius NH Paerregaard A Michaelsen KF Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis J Pediatr 2004145(5)612ndash616
9 zajewska H Ruszczyński M Radzikowski A Probiotics in the prevention of antibiotic-associated diarrhea in children a meta-analysis of randomized controlled trials J Pediatr 2006149(3)367ndash372
10 BENJAMIN KLIGLER MD MPH Albert Einstein College of Medicine of Yeshiva University New York New York ANDREAS COHRSSEN MD Beth Israel Residency Program in Urban Family Practice New York New York Probiotics Am Fam Physician 2008 Nov 178(9)1073-1078
Thank you
Thank you
![Prevention of Food Allergy...Probiotics in Prevention of Food Allergy Human study [Kalliomaki et al 2001] • Mothers given lactobacillus GG antenatally • Infants given oral lactobacillus](https://img.dokumen.tips/doc/110x75/5ea64f7814260365206ee28a/prevention-of-food-probiotics-in-prevention-of-food-allergy-human-study-kalliomaki.jpg)
