MARY ELLEN SANDERS, PH.D.

E X E C U T I V E S C I E N C E O F F I C E R , I N T E R N A T I O N A L S C I E N T I F I C A S S O C I A T I O N F O R P R O B I O T I C S A N D P R E B I O T I C S

( W W W . I S A P P S C I E N C E . O R G )

A P R I L 2 5 , 2 0 1 7

S Y M P O S I U M : “ P R O B I O T I C S , T H E I R R O L E I N H E A L T H .

A V I S I O N F R O M T H E S O U T H E R N C O N E ”

B U E N O S A I R E S , A R G E N T I N A

Probiotics: Their Benefits and Uses

ISAPP Annual Meeting “Key Scientific Drivers Behind Probiotic and Prebiotic Applications”

Program and Registration: www.isapp2018.org

Microbes associated with the human body are important to health

Our colonizing microbes impact:

Food digestion

Immune system development

Endocrine function

Energy homeostasis

Fat storage

Blood lipids

Brain signaling

Gut integrity and function

Our modern microbiota may be deficient

Modern lifestyles may negatively impact our microbiota• Antibiotics and other drugs• C-section births• Reduced breast feeding• Sanitation• Diets with ↓live microbes, ↓ fiber• Reduced living around animals

Microbiota generally stabilizes ~2 years of age, but can change:• As we age• In response to short or long term perturbations

o Dieto Environmento Antibiotics, drugs

• Disease state (associations, not causality)

Many diseases/disorders are associated with an altered microbiome

Atopy and asthma

Celiac disease

Colon cancer

Diabetes

HIV infection

Ulcerative colitis

Irritable bowel syndrome

Gastroenteritis

Necrotizing enterocolitis

Obesity

Rheumatoid arthritis

Liver disease

Microbiota of healthy subjects differ from subjects with these conditions

Causality has not been determined

Dietary strategies to support gut microbiota

Fibers

Increase overall microbial numbers and diversity

Prebiotics

Selectively increase beneficial bacterial populations or activities

Probiotics

Fermented foods

Probiotics

Live microorganisms that, when administered in adequate amounts, confer

a health benefit on the host

Photo, courtesy of G. Gibson

FAO/WHO (2001) Expert Consultation ftp://ftp.fao.org/docrep/fao/009/a0512e/a0512e00.pdf

As revised by Hill et al. 2014The International Scientific Association for Probiotics and Prebiotics consensus

statement on the scope and appropriate use of the term probioticNature Rev Gastroenterol Hepatol. 11, 506–514.

Fermented Foods

Fermented foods are foods resulting from the growth and metabolism of live cultures,

transforming a precursor food (such as milk) into a fermented food (cheese)

Fermented foods are often referred to as ‘probiotics’

But there are some important ways that probiotics and fermented foods differ

Probiotic Fermented Food

Made by live microbes, but live microbes may not survive (post-fermentation processing)

May not have been tested for health benefits

Likely healthy dietary components, but may not be probiotics

Must contain live microbes

Must be tested and shown to have health benefit

Must deliver level of live microbes shown to confer benefit

Fermented food vs. probiotic

When a fermented food contains live microbes at sufficient levels to confer a known benefit, then it is correct to call it a “probiotic”.

Microbial Species Used as Probiotics

Lactobacillus

Bifidobacterium

Saccharomyces

Enterococcus

Bacillus

Images courtesy of Prof. Lorenzo Morelli

As we learn more about normal, colonizing

bacteria, this range of probiotic microbes likely to

expand

Not all probiotics are the same

Equus caballusSame species, different function

For probiotics:Lactobacillus acidophilus NCFM

genus species strain

Do probiotics colonize?

Probiotics can be isolated from feces after oral administration is stopped Typically 1-2 weeks: very temporary ‘colonization’

Dose and strain dependent

Most probiotics cannot be isolated from feces long term

Infants may retain longer More available niches?

Growth/replication in vivo will extend length of presence

Biopsy studies sometimes show longer persistence than fecal samples

Notable exception: stably colonizing B. longum

Probiotics health benefits

Number Needed to Treat for Probiotics Used in Different Clinical Indications

NNT = average number of patients who need to be treated to prevent one additional bad outcome

Endpoint Population NNT Probiotic

Incidence AAD Pediatric 7 L. rhamnosus GGS. boulardii

Incidence AAD Adult, hospitalized 9 BioK+

Incidence C. difficile diarrhea

Pediatric+adult, hospitalized

41 S. boulardii

Incidence C. difficile diarrhea

Adult, hospitalized 30 BioK+

Crying time Colicky, breastfed infants

3 L. reuteri DSM17938

Incidence severe NEC Premature infants 30 Different strains

Incidence death due to NEC

Premature infants 41 Different strains

Extend remission of UC Adults 8 VSL#3

Adapted from Merenstein et al. Manuscript in preparation

Effect Size

Probiotics may decrease duration of acute diarrhea in infants and children by ~1 day

Probiotics administered prenatally and postnatally may reduce the relative risk of food hypersensitivity by 23%

Probiotics during late pregnancy and lactation (after 36th week of pregnancy and the first months of lactation) may reduce the relative risk of eczema by 22%

Probiotics may reduce the relative risk of developing severe NEC by 57% and mortality by 35%

Probiotics may reduce mean episode duration of respiratory tract infections by 1.9 days, antibiotic use and cold-related school absences

Merenstein, Medscape CME, April 2018

M o d e rate q u a l i t y e v i d e n c e s u g g e st s t h at i n fa n t s a n d c h i l d re n w h o a re g i ve n Lac tobac i l l u s a n d /o r

B i f i dobac te r ium to p re ve n t a c u te re s p i ra to r y t ra c t i n fe c t i o n s a n d a c u te l o w e r d i g e st i ve t ra c t i n fe c t i o n s h ave a d e c re a s e d r i s k o f b e i n g

p re s c r i b e d a n t i b i o t i c s .

Does probiotic consumption reduce antibiotic utilization for common acute

infections? A systematic reviewSarah King, Kelsie Gould, Hailey Vann, Grant Connors, Daniel Tancredi, Irene Lenoir-Wijnkoop, Mary Ellen Sanders, Jeffrey Linder, Andi Shane,

Dan Merenstein

Manuscript submitted to Int J Epidemiol

Promotion of resilience may also be a health benefit of probiotics

Restoration of the gut microbiota following perturbation may help prevent microbiota-associated disorders

Evidence for this mechanism by probiotics is needed

Link to clinical benefits?

Sanders et al. 2011.Gut Microbes 2:1-7.

Can health of our microbiota be promoted by diet?

Probiotics, fermented foods, and prebiotics may provide a safe approach to dietary management of some microbiota-associated health challenges of public health significance

Studies of probiotics in healthy people have shown benefits for: Immune support

Intestinal health

Reduce common infections

Reduce antibiotic use

Blood lipids

Even small magnitudes of effect can have a big impact on public health.

What you need to know to make smart choices with probiotics

How to choose a probiotic

Decision should be based on:

Your health needs

Evidence that a specific probiotic has a benefit

Remember: strain matters

Responsible manufacturing and quality

Some considerations

Not all fermented foods are probiotics

Products with many strains are not necessarily better

Products with high doses are not necessarily better

Foods and supplements can both be good sources of probiotics

If you have a health concern, choose a probiotic studied for that

problem and shown to be beneficial

Recommendations for use of probiotics

European Society for Primary Care

Gastroenterology

European Society for PaediatricGastroenterology, Hepatology and

Nutrition

World Gastroenterology Organisation

World Allergy

Organization

Evidence assessment for products in USA-updated yearlyIndustry-funded but independently conducted

http://usprobioticguide.com/Funded by unrestricted education grant from Bio-K+, Integra Medical, P&G

Professional, Gerber, Jarrow Formula, GenestraAlliance for Education on Probiotics http://www.aeprobio.com/

Different people may respond differently

Diet

Colonizing microbiota

Individual characteristics of each person

http://ehp.niehs.nih.gov/121-a276/

If you do not have a specific health concern:

Consider probiotics shown to have benefits for healthy people

Consider fermented foods, probiotic foods, prebiotics, fiber

ISAPP Infographics

ISAPP Videos

Key points

Our colonizing microbiota are important to our health

Dietary strategies to help support our gut microbiota include:

Fiber, prebiotics, probiotics, fermented foods

Fermented foods may contain live microbes but might not have been studied for health benefits Not all fermented foods are probiotic foods

Heath benefits for probiotics include therapeutic benefits and benefits for generally healthy people

When choosing a probiotic, let evidence of health benefit be your guide Some evidence-based guidelines available

If evidence-based products are not available, may need to resort to trial and error

Individuals respond differently to probiotics

See ISAPP materials for further information www.ISAPPscience.org ISAPP Infographics, videos, blogs