Probiotics and Prebiotics as Functional Ingredients in Inflammatory Bowel Disease

7/28/2019 Probiotics and Prebiotics as Functional Ingredients in Inflammatory Bowel Disease

1/13

Volume 43 Number 6 2008

Nutrition Today Page 1

Probiotics and Prebiotics asFunctional Ingredients inInflammatory Bowel DiseaseMirjam A.C. Looijer-van Langen MD

Vimal Prajapati

Levinus A. Dieleman MD, PhD

Nutrition Today

November/December 2008

Volume 43 Number 6

Pages 235 - 242

Abstract

Probiotics and prebiotics are promising nutraceuticals that may exert a beneficial effect in many medicalconditions including inflammatory bowel disease. With the increasing occurrence of antibiotic

resistance, the search for medication with little side effects, and the need for options for patients with

inflammatory bowel disease who are unresponsive to current therapies, research into alternative

therapeutic options is justified. Preclinical studies have provided insights into the effects of probiotics

and prebiotics on the immune system and gut microbiota. This new information, along with the older

evidence, shows that probiotics and prebiotics may ameliorate chronic intestinal inflammation. This

article gives a short overview on current knowledge of probiotics and prebiotics.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders that include Crohn disease (CD),ulcerative colitis (UC), and chronic pouchitis. Crohn disease can affect the entire gastrointestinal tract

anywhere from mouth to anus. The chronic inflammation is not limited to the lining of the bowel but

affects the entire bowel wall, sometimes resulting in intra-abdominal abscesses and fistula (abnormal

connections between the lumen of the bowel, other organs, or the surface of the skin) and intestinal

obstruction. Patients typically experience symptoms of mild diarrhea, right lower quadrant pain, and

low-grade fever. Ulcerative colitis is limited to the colon, and patients experience rectal bleeding,

abdominal pain, and diarrhea. The inflammation in UC is confined to the upper layer of the colonic wall

and the mucosa. Patients with CD and those with UC both experience periods of remission and relapses.

Chronic pouchitis is a chronic inflammation of the ileoanal pouch. An ileoanal pouch is an internal

reservoir, constructed for patients with UC who have had their large intestine surgically removed mostly

because of severe inflammation refractory to medical treatment. Patients with pouchitis typically

present with bloody diarrhea, urgency in passing stools, or discomfort while passing stools. Rarely, pain

occurs with pouchitis.

Inflammatory bowel disease is caused by multiple factors that disturb intestinal homeostasis. An

abnormal immune response to commensal bacteria or dietary factors in genetically susceptible hosts

plays a major role in the pathogenesis. Environmental factors including psychological stress, use of

nonsteroidal anti-inflammatory drugs, and cigarette smoking can also contribute to IBD. The current

treatment of IBD mainly consists of drugs directed against the overactive adaptive immune response,


2/13



such as 5-aminosalicylic acid compounds, steroids, azathioprine/6-mercaptopurine, methotrexate,

cyclosporine, and biologics such as infliximab. Most patients respond well to these medications, but for

some, it is inadequate or induces intolerable adverse effects. Therefore, interest has been raised in

nutraceutical therapies such as probiotics, prebiotics, or a combination of these, called synbiotics, as a

good therapeutic option for nonresponding patients with IBD.

Theconcept that ingestion of certain bacteria may promote health is not new. Fermented milk products

have been consumed by human beings for thousands of years with the belief that they provide health

benefits. For example, according to Persian tradition, Abraham of the Old Testamentowed his

longevity to sour milk.

In the early 20th century, the Russian immunologist, Elie Metchnikoff, proposed that ingestion of

lactic acid bacteria promoted health and longevity of life. He based his theory on the observation that

Bulgarians who consumed large quantities of fermented milk lived longer than those who did not.

Around the same time, the first attempt to treat disease with bacteria was made by Dr Henry Tissier, a

French pediatrician, who discovered Y-shaped or "bifid" bacteria (now known as Bifidobacterium) and

recommended administration of isolated bifid cultures to infants with diarrhea to help restore ahealthy gut flora. Metchnikoff and Tissier are largely credited for being the first individuals to make

scientific suggestions about probiotic bacteria, although the termprobioticwas not coined until 1965.

The termprobiotic, which literally means "for life," was first introduced by Lilly and Stillwell in 1965 to

describe "substances produced by one microorganism which stimulate the growth of another." Since

that time, the definition has undergone many revisions. In an attempt to provide an agreed upon

definition, a joint Food and Agricultural Organization/World Health Organization Expert Consultation
http://adsoftheworld.com/media/print/wwf_seal_0?size=_original


3/13



redefined probiotics as "live microorganisms which when administered in adequate amounts confer a

health benefit on the host." Currently, this is the most widely accepted definition.

Probiotics can be bacteria or yeast, although the vast majority is bacteria. The most common bacteria

used as probiotics are lactic acid bacteria from the genera Lactobacillus and Bifidobacterium. Certain

species from other genera such as Streptococcus, Enterococcus, and Escherichia have also been usedbut to a lesser extent. The only yeast that is considered a probiotic is Saccharomyces boulardii(Table

1). Probiotics are available in a variety of food products, especially dairy products such as yogurt, milk,

cottage cheese, and dietary supplement products. Dietary supplements containing freeze-dried

probiotics in capsule, powder, or tablet form are becoming a popular choice.

Table 1. Common Probiotic Organisms

Multiple mechanisms of action have been postulated to account for the beneficial effects of probiotics

in IBD. In broad terms, probiotics are thought to improve the epithelial barrier function of the

intestine, alter the composition of the intestinal microflora, and modulate the immune response of

the intestinal mucosa. However, the exact mechanism is likely to vary from one probiotic organism toanother (Table 2).

Table 2. Proposed Benefits of Probiotics to the Well-being and Health of the Animal

Host

Normal epithelial barrier function of the intestine requires an intact layer of epithelial cells and an

adequate production of overlying mucus to prevent uptake of potentially harmful organisms and

substances into the body. A disrupted and leaky intestinal epithelial barrier may be one of the

initiating events in the pathogenesis of IBD. In addition, increased apoptosis (programmed cell death)

of intestinal epithelial cells and decreased mucus production have been documented in patients with

IBD and are thought to contribute to the pathogenesis. Several probiotics have demonstrated theability to enhance the epithelial barrier function of the intestine. For example, Lactobacillus

rhamnosus GG improves barrier function by inhibiting apoptosis of intestinal epithelial cells.

Streptococcus salivarius subsp thermophilus and Lactobacillus acidophilus have been shown to

enhance the tight junctions between epithelial cells, thereby preventing infection from the invasion of

pathogenic bacteria such as enteroinvasive Escherichia coli. Also, several Lactobacillus strains have

been found to increase mucus production. Madsen showed that a synthetic probiotic mixture, VSL#3

(containing 4 Lactobacillus spp, 3 Bifidobacterium spp, and S salivarius subsp thermophilus), also

restored the epithelial barrier function in a chronic colitis mouse model. The improvement of the

barrier function is probably the result of a direct effect of probiotic bacteria or their secreted bacterial

products.

Normally, there is a balance between the beneficial bacterial species and the detrimental bacterial

species that make up the intestinal microflora. In IBD, a number of genetic and environmental factors

are thought to upset this balance such that there is a relative predominance of detrimental disease-

inducing bacteria that contribute to the chronic inflammatory process in IBD. Probiotics can help

restore a healthy intestinal microflora by directly increasing the population of beneficial bacteria and

by suppressing the growth and function of detrimental bacteria. For example, Bifidobacterium infantis
http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT2http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT2http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT2http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT2http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT1


4/13



has been shown to suppress the growth ofBacteroides vulgatus, a pathogenic microbe possibly

responsible for the induction and perpetuation of IBD.

Probiotic organisms can inhibit pathogenic bacteria in several ways. First of all, they competitively

exclude pathogens by occupying the limited physical space available for colonization in the gut. In

addition, probiotic organisms can either directly secrete antimicrobial substances (eg, organic acids,hydrogen peroxide, and bacteriocins) and/or stimulate host intestinal cells to secrete antimicrobial

substances (ie, defensin molecules), which destroy pathogens before they can colonize the gut.

Several probiotics have demonstrated the ability to prevent epithelial adhesion and invasion of

pathogenic bacteria. For example, E coliNissle 1917 inhibits epithelial adhesion and invasion of a

pathogenic E colistrain isolated from patients with CD.

Inflammatory bowel disease is thought to be caused by an overly aggressive immune response to the

endogenous gut microflora in genetically susceptible individuals. This results in an increased

production of chemical signals that promote inflammation. These proinflammatory cytokines include,

for example, tumor necrosis factor [alpha] and interferon [gamma]. Anti-inflammatory cytokines are

interleukin 10 and transforming growth factor [beta]. Probiotic organisms are generally thought tomodify the immune system of the intestinal mucosa by reducing the production of proinflammatory

cytokines and increasing the production of anti-inflammatory mediators. Studies have shown that

Lactobacillus plantarum, L rhamnosus GG, and VSL#3 can increase the production of interleukin 10

and that specific lactobacilli and bifidobacteria species can reduce the production of tumor necrosis

factor [alpha] and interferon [gamma]. The mechanisms by which probiotics exert their

immunomodulatory effects are complex and beyond the scope of this review.

Probiotics are generally well tolerated and have an excellent overall safety record. This is not

surprising because many of the organisms used as probiotics are commensal, nonpathogenic

inhabitants of the human gut and have been used safely in the production of fermented foods for

centuries. The most common adverse effects of probiotics include bloating, flatulence, and

constipation. There have been some reports of probiotics inducing serious infections such as bacterial

and fungal sepsis. However, these cases occurred in immunocompromised patients. There are no

reports of such cases in healthy people.

Animal models have been used extensively to study the efficacy of probiotics in treating chronic

intestinal inflammation and to elucidate the mechanisms by which probiotics work. Successful

reduction of intestinal inflammation in many of these experimental models has provided the support

for human clinical trials (Table 3). Escherichia coliNissle 1917, VSL#3, and bifidobacteria-fermented

milk have been shown to have some success at inducing and maintaining remission of UC and

reducing disease activity.

Table 3. Clinical Studies Testing Probiotics in the Treatment of Human Inflammatory

Bowel Disease

VSL#3 proved to be effective in maintaining remission of chronic relapsing pouchitis, preventing the

development of pouchitis compared with placebo treatment; in addition, it also significantly improved

patient quality of life. One study with L rhamnosus GG, however, was ineffective in reducing pouchitis

disease activity.
http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT3http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT3http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT3http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT3


5/13



The efficacy of probiotics in CD is still controversial. For example, Lactobacillus salivarius, VSL#3, and S

boulardiiin combination with conventional therapy (mesalamine) have had some success. On the

other hand, there are numerous studies reporting the ineffectiveness of various probiotics in CD.

Because the viability of probiotics in some food products and during transit through the

gastrointestinal tract is variable, the prebiotic concept has been developed. Prebiotics arenondigestible short-chain carbohydrates, originally defined as selectively fermented ingredients that

allow specific changes, both in the composition and/or activity in the gastrointestinal microflora that

confer benefits upon host's well-being and health.

Substances are considered prebiotics according to the following conditions:

(1) when they are not broken down nor absorbed by enzymes in the upper part of the mammalian

gastrointestinal tract,

(2) when they are selectively fermented by one or a limited number of potentially beneficial bacteria

in the intestine, and

(3) when they are able to alter the colonic microflora toward a healthier composition.

Prebiotics have become very popular food ingredients. The most commonly used prebiotics, inulin

and oligofructose, are natural food ingredients or dietary fibers present in plants as storage

carbohydrates. Wheat, chicory, bananas, onions, leeks, Jerusalem artichokes, asparagus, and garlic

contain prebiotics. Most commercially used prebiotics are synthesized from sucrose or extracted from

chicory roots. They are used in, for example, confectioneries, bakery products, fruit juices, desserts,
http://maxcdn.creativeadawards.com/wp-content/uploads/2009/11/Polar-bear-o.jpg


6/13



spreads, taste improver, sweetener, and fat replacers and sometimes used as viscosity-increasing

agents.

Inulin and oligofructose, also called [beta]-fructans, are composed of fructose units joined by [beta]-

glycosidic links. Because of their different fructose chain lengths, inulin and oligofructose are used for

different purposes. Inulin has a longer chain length and is therefore less soluble and suitable as a fatreplacer.

Oligofructose is composed of a shorter chain length of fructose molecules and is, for example, used to

replace sugar. Depending on the diet, the daily intake of prebiotics in Western societies varies from 3

to 13 g per day.

Many substances are claimed to have prebiotics effects but only fructo-oligosaccharides, galacto-

oligosaccharides, lactulose, and inulin have been shown to meet all 3 before mentioned criteria. Other

potential prebiotic candidates are mentioned inTable 4.

Table 4. Potential Candidate Prebiotic Substrates

Different medical conditions have been speculated to ameliorate upon treatment with prebiotics,

including improvement of mineral absorption, reduced risk for colon cancer, improvement of food

allergies, alleviation of constipation, regulation of lipid metabolism, and reduction of antibiotic-

induced diarrhea.

The working mechanisms of prebiotics are not fully understood yet, but many theories have been

formed (Table 5). In broad terms, the beneficial effects are believed to be due to the stimulation of

protective intestinal organisms and the production of short-chain fatty acids (SCFAs) as fermentation

products of prebiotics.

Table 5. Proposed Benefits of Prebiotics to the Well-being and Health of the Animal

Host

The intestinal barrier functions to protect the individual from potential bacterial threats. The mucus

layer in the gastrointestinal tract plays a major role by preventing the attachment and translocation of

bacteria across the epithelial wall. A decrease in mucus production is seen in IBD. Prebiotics have

been shown to increase the mucus layer in a rat model of colitis.

As mentioned before, intestinal bacteria play an important role in the pathogenesis and attenuation

of IBD. Prebiotics change the intestinal microflora in animal models and human studies by increasing

the numbers of intestinal protective bacteria, for example, lactobacilli and bifidobacteria, anddecreasing the proportion of pathogenic bacteria. Several studies performed in infants confirmed this,

showing that the intestinal microbiota of breast-fed infants (containing milk oligosaccharides) is

generally dominated by bifidobacteria and lactic acid bacteria. In contrast, formula-fed infants'

intestinal microflora contains lower numbers of bifidobacteria and lactic acid bacteria and contains

more bacteroides, clostridia, and enterobacteriaceae. However, after the prebiotic diet is stopped,

these microflora changes gradually return to baseline levels.
http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT4http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT4http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT4http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT5http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT5http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT5http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT5http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT4


7/13



Short-chain fatty acids include butyrate, acetate, and propionate. Butyrate is the major energy source

for colonic epithelial cells and plays an essential role in the maturation of colonic epithelium,

regeneration of mucosa, induction of epithelial cell differentiation, and stimulation of their apoptosis.

A reduced level of luminal SCFAs may play a role in the onset of IBD. The amount of SCFAs produced in

the colon depends on the composition of intestinal microflora, their substrates, and the gut transit

time. Fermentation of prebiotics by colon bacteria results in higher luminal SCFA production, whichresults in acidification of the colonic content. Intraluminal acidification may inhibit the growth of

harmful or disease-inducing bacteria.

Several studies show that the prebiotic effects are different for each prebiotic substance and that

these depend on intestinal pH, prebiotic dosages, intraluminal concentrations of prebiotics, duration

of intake, locations in the gut where fermentation occurs, and composition of endogenous intestinal

microflora.

Prebiotics have been part of human diets for centuries and are generally recognized as safe to

consume. However, they can cause symptoms of abdominal pain, eructation, flatulence, bloating,

abdominal cramps, and diarrhea. There are some reports of increased bacterial translocation ofpathogenic bacteria during prebiotic treatment, such as Salmonella, and in sepsis models, but these

results are controversial and are not seen in patients. More research in this area is needed.

The effects of prebiotics are most extensively studied in different rodent models of IBD. Various

efficacy of prebiotics and synbiotics (combination of probiotics and prebiotics) in different IBD models

was found, but in most studies, prebiotics seem to ameliorate intestinal inflammation. Inulin, starch,

lactulose, combination of oligofructose and inulin, and goat milk oligosaccharides reduced colitis.

Some fructo-oligosaccharides showed mixed results, whereas galacto-oligosaccharides failed to

reduce intestinal inflammation.

Currently, only a few studies with prebiotics in patients with IBD have been published. Emerging small

short-term studies using prebiotics or synbiotics showed reduction of inflammation in patients with

pouchitis, UC, and CD (Table 6). A small open-label study in patients with active ileocolonic CD treated

with a combination of oligofructose and inulin showed a significant reduction in disease activity. A

recent pilot study investigated the adjunct effect of oligofructose-enriched inulin in patients with mild

to moderate UC with concomitant 5-aminosalicylic acid treatment (n = 19). This placebo-controlled

study reported a significant reduction of fecal calprotectin (marker of intestinal inflammation) in the

prebiotic-treated patients compared with the placebo group, suggesting that these prebiotics reduced

chronic intestinal inflammation.

Table 6. Clinical Studies Testing Prebiotics or Synbiotics in the Treatment of Human

Inflammatory Bowel Disease

A randomized double-blind crossover study in pouchitis patients after colectomy for UC treated with

inulin resulted in the reduction of mucosal inflammation However, Chermesh et al could not show

prevention of relapse of CD after surgical resection with synbiotic treatment, although this study may

be underpowered.

Conclusion and Future Perspectives
http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT6http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT6http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT6http://www.nursingcenter.com/library/journalarticleprint.asp?Article_ID=833424#TT6


8/13



Probiotics and prebiotics are emerging as promising therapeutic options for the treatment and

prevention of flare-ups of IBD. A significant number of studies in both animal models and human IBD

have documented the efficacy of these therapies in ameliorating chronic intestinal inflammation. In

addition, these studies have led to a greater understanding of the mechanisms by which probiotics

and prebiotics exert their beneficial effects. However, it is important to remember that the

mechanisms elucidated cannot be generalized, as not all probiotics and prebiotic have similartherapeutic effects. Probiotics and prebiotics are widely available, are easy to consume, and are

recognized as safe to consume. Side effects are rare, but some adverse effects such as bloating and

flatulence tend to limit subsequent intake. The results obtained thus far warrant further rigorous well-

designed and larger clinical trials to firmly establish the safety and efficacy of probiotics and prebiotics

in IBD.

REFERENCES

1. Boyle RJ, Robins-Browne RM, Tang MLK. Probiotic use in clinical practice: what are the risks?Am J

Clin Nutr. 2006;83:1256-1264.

2. Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics-approaching a definition.Am J

Clin Nutr. 2001;73(suppl):361S-364S.

3. Metchnikoff E. The prolongation of life: optimistic studies. London, England: Butterworth-

Heinemann; 1907.

4. FAO/WHO. Health and nutritional properties in food including powder milk with live lactic acid

bacteria. 2001.http://www.fao.org/ag/agn/agns/micro_probiotics_en.asp . Accessed June 9, 2007.

5. Lilly DM, Stillwell RH. Probiotics: growth promoting factors produced by microorganisms. Science.

1965;147:747-748.

6. Baumgart DC, Carding SR. Inflammatory bowel disease: cause and immunobiology. Lancet.

2007;369:1627-1640.

7. Yan F, Polk DB. Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial

cells.J Biol Chem. 2002;277:50959-50965.

8. Resta-Lenert S, Barrett KE. Live probiotics protect intestinal epithelial cells from the effects of

infection with enteroinvasive Escherichia coli(EIEC). Gut. 2003;52:988-997.

9. Mack DR, Michail S, Wei S, et al. Probiotics inhibit enteropathogenic E. coliadherence in vitro by

inducing intestinal mucin gene expression.Am J Physiol. 1999;276:G941-G950.

10. Madsen KL. Inflammatory bowel disease: lessons from the IL-10 gene-deficient mouse. Clin Invest

Med. 2001;24:250-257.

11. Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat

Rev Immunol. 2003;3:521-533.
http://www.fao.org/ag/agn/agns/micro_probiotics_en.asphttp://www.fao.org/ag/agn/agns/micro_probiotics_en.asphttp://www.fao.org/ag/agn/agns/micro_probiotics_en.asphttp://www.fao.org/ag/agn/agns/micro_probiotics_en.asp


9/13



12. Shiba T, Aiba Y, Ishikawa H, et al. The suppressive effect of bifidobacteria on Bacteroides vulgatus,

a putative pathogenic microbe in inflammatory bowel disease. Microbiol Immunol. 2003;47:371-378.

13. Fedorak RN, Madsen KL. Probiotics and the management of inflammatory bowel disease. Inflamm

Bowel Dis. 2004;10:286-299.

14. Boudeau K, Glasser AL, Julien S, et al. Inhibitory effect of probiotic Escherichia colistrain Nissle

1917 on adhesion and invasion of intestinal epithelial cells by adherent-invasive E. colistrains isolated

from patients with Crohn's disease.Aliment Pharmacol Ther. 2003;18:45-56.

15. Ulisse S, Gionchetti P, D'Alo S, et al. Expression of cytokines, inducible nitric oxide synthase, and

matrix metalloproteinases in pouchitis: effects of probiotic treatment.Am J Gastroenterol.

2001;96:2691-2699.

16. Dieleman LA, Goerres MS, Arends A, et al. Lactobacillus GG prevents recurrence of colitis in HLA-

B27 transgenic rats after antibiotic treatment. Gut. 2003;52:370-376.

17. Madsen KI, Doyle JS, Jewell LD, et al. Lactobacillus species prevents colitis in interleukin 10 gene-

deficient mice. Gastroenterology. 1999;116:1107-1114.

18. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in

patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology.

2000;119:305-309.

19. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a

double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202-1209.

20. Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (VSL#3) formaintaining remission in recurrent and refractory pouchitis. Gut. 2004;53:108-114.

21. Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coliversus mesalazine

for the treatment of ulcerative colitis: a randomised trial. Lancet. 1999;354:635-639.

22. Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic

Escherichia coliNissle 1917 is as effective as with standard mesalazine. Gut. 2004;53:1617-1623.

23. Bibiloni R, Fedorak RN, Tannock GW, et al. VSL#3 probiotic-mixture induces remission in patients

with active ulcerative colitis.Am J Gastroenterol. 2005;100:1539-1546.

24. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new

probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis.

Aliment Pharmacol Ther. 1999;13:1103-1108.

25. Kato K, Mizuno S, Umesaki Y, et al. Randomized placebo-controlled trial assessing the effect of

bifidobacteria-fermented milk on active ulcerative colitis.Aliment Pharmacol Ther. 2004;20:1133-

1141.


10/13



26. Ishikawa H, Akedo I, Umesaki Y, et al. Randomized controlled trial of the effect of bifidobacteria-

fermented milk on ulcerative colitis.J Am Coll Nutr. 2003;22:56-63.

27. McCarthy K, O'Mahony L, Dunne C. An open trial of a novel probiotic as an alternative to steroids

in mild/moderately active Crohn's disease. Gut. 2001;49(suppl III):A2447.

28. Campieri M, Rizzello F, Venturi A. Combination of antibiotic and probiotic treatment is efficacious

in prophylaxis of postoperative recurrence of Crohn's disease: a randomised controlled trial with

Lactobacillus GG. Gastroenterology. 2000;118:A781.

29. Guslandi M, Mezzi G, Sorghi M, et al. Saccharomyces boulardiiin maintenance treatment of

Crohn's disease. Dig Dis Sci. 2000;45:1462-1464.

30. Kuisma J, Mentula S, Jarvinen J, et al. Effect ofLactobacillus rhamnosus GG on ileal pouch

inflammation and microbial flora.Aliment Pharmacol Ther. 2003;17:509-515.

31. Marteau P, Lemann M, Seksik P, et al. Ineffectiveness ofLactobacillus johnsoniiLA1 forprophylaxis of postoperative recurrence in Crohn's disease: a randomised, double blind, placebo

controlled GETAID trial. Gut. 2006;55:842-847.

32. Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing

recurrence after curative resection for Crohn's disease: a randomised controlled trial with

Lactobacillus GG. Gut. 2002;51:405-409.

33. Bousvaros A, Guandalini S, Baldassano RN, et al. A randomized, double-blind trial ofLactobacillus

GG versus placebo in addition to standard maintenance therapy for children with Crohn's disease.

Inflamm Bowel Dis. 2005;11:833-839.

34. Schultz M, Timmer A, Herfarth HH, Sartor RB, Vanderhoof JA, Rath HC. Lactobacillus GG in inducing

and maintaining remission of Crohn's disease. BMC Gastroenterol. 2004;4:5.

35. Prantera C, Scribano ML. Probiotics and Crohn's disease. Dig Liver Dis. 2002;34(suppl 2):S66-S67.

36. Roberfroid M. Prebiotics: the concept revisited.J Nutr. 2007;137:830S-837S.

37. Gibson G, Roberfroid M. Dietary modulation of the human colonic microflora: introducing the

concept of prebiotics.J Nutr. 1995;125:1401-1412.

38. Swennen K, Courtin CM, Delcour JA. Non-digestible oligosaccharides with prebiotic properties. CRC

Crit Rev Food Sci Nutr. 2006;46:456-471.

39. Niness K. Inulin and oligofructose: what are they?J Nutr. 1999;129:1402S-1406S.

40. Delzenne N, Cherbut C, Neyrincka A. Prebiotics: actual and potential effects in inflammatory and

malignant colonic diseases. Curr Opin Clin Nutr Metab Care. 2003;6:581-586.


11/13



41. Cherbut C. Inulin and oligofructose in the dietary fibre concept. Br J Nutr. 2002;87(suppl 2):S159-

S162.

42. Gibson GR, Probert HM, Van Loo J, et al. Dietary modulation of the human colonic microbiota:

updating the concept of prebiotics. Nutr Res Rev. 2004;17:259-275.

43. Macfarlane S, Macfarlane GT, Cummings JH. Review article: prebiotics in the gastrointestinal tract.

Aliment Pharmacol Ther. 2006;24:701-714.

44. Korzenik JR, Podolsky DK. Evolving knowledge and therapy of inflammatory bowel disease. Nat

Rev Drug Discov. 2006;5:197-209.

45. Gibson GR. Dietary modulation of the human gut microflora using the prebiotics oligofructose and

inulin.J Nutr. 1999;129(suppl S):1438s-1441s.

46. Fontaine N, Meslin JC, Lory S, et al. Intestinal mucin distribution in the germ-free rat and in the

heteroxenic rat harbouring a human bacterial flora: effect of inulin in the diet. Br J Nutr. 1996;75:881-892.

47. Gibson GR, Beatty ER, Wang X. Selective stimulation of bifidobacteria in the human colon by

oligofructose and inulin. Gastroenterology. 1995;108:975-982.

48. Coppa GV, Zampini L, Galeazzi T, et al. Prebiotics in human milk: a review. Dig Liver Dis.

2006;38(suppl 2):S291-S294.

49. Bouhnik Y, Raskine L, Simoneau G, et al. The capacity of nondigestible carbohydrates to stimulate

fecal bifidobacteria in healthy humans: a double-blind, randomized, placebo-controlled, parallel-

group, dose-response relation study 1-3.Am J Clin Nutr. 2004;80:1658-1664.

50. Wong JMW, Russell de Souza RD, et al. Colonic health: fermentation and short chain fatty acids.J

Clin Gastroenterol. 2006;40:235-243.

51. Ten Bruggencate SJM, Bovee-Oudenhoven IMJ, Lettink-Wissink MLG, et al. Dietary fructo-

oligosaccharides and inulin decrease resistance of rats to Salmonella: protective role of calcium. Gut.

2004;53:530-535.

52. Videla S, Vilaseca J, Antol[latin dotless i]n M, et al. Dietary inulin improves distal colitis induced by

dextran sodium sulfate in the rat.Am J Gastroenterol. 2001;96:5.

53. Moreau NM, Martin LJ, Toquet CS, et al. Restoration of the integrity of rat caeco-colonic mucosa

by resistant starch, but not by fructo-oligosaccharides, in dextran sulfate sodium-induced

experimental colitis. Br J Nutr. 2003;90:75-85.

54. Rumi G, Tsubouchi R, Okayama M, et al. Protective effect of lactulose on dextran sulfate sodium-

induced colonic inflammation in rats. Dig Dis Sci. 2004;49:1466-1472.


12/13



55. Hoentjen F, Welling GW, Harmsen HJM, et al. Reduction of colitis by prebiotics in HLA-B27

transgenic rats is associated with microflora changes and immunomodulation. Inflamm Bowel Dis.

2005;11:11.

56. Daddaoua A, Puerta V, Requena P, et al. Goat milk oligosaccharides are anti-inflammatory in rats

with hapten-induced colitis.J Nutr. 2006;136:672.

57. Holma R, Juvonen P, Asmawi MZ, et al. Galacto-oligosaccharides stimulate the growth of

bifidobacteria but fail to attenuate inflammation in experimental colitis in rats. Scand J Gastroenterol.

2002;37:1042-1047.

58. Welters CFM, Heineman E, Thunissen FBJM, et al. Effect of dietary inulin supplementation on

inflammation of pouch mucosa in patients with an ileal pouch-anal anastomosis. Dis Colon Rectum.

2002;45:621-627.

59. Furrie E, Macfarlane S, Kennedy A, et al. Synbiotic therapy (Bifidobacterium longum/synergy 1)

initiates resolution of inflammation in patients with active ulcerative colitis: a randomised controlledpilot trial. Gut. 2005;54:242-249.

60. Lindsay JO, Whelan K, Stagg AJ, et al. Clinical, microbiological, and immunological effects of fructo-

oligosaccharide in patients with Crohn's disease. Gut. 2006;55:348-355.

61. Chermesh I, Tamir A, Reshef R, et al. Failure of synbiotic 2000 to prevent postoperative recurrence

of Crohn's disease. Dig Dis Sci. 2007;52:385-389.

62. Casellas F, Norruel N, Torrjeo A, et al. Oral oligofructose-enriched inulin supplementation in acute

ulcerative colitis is well tolerated and associated with lowered faecal calprotectin.Aliment Pharmacol

Ther. 2007;25:1061-1067.

Copyright 1996-2004 Lippincott Williams & Wilkins, Inc., A Wolters Kluwer Company. All rights

reserved.


13/13



Documents

Probiotics and Prebiotics as Functional Ingredients in Inflammatory Bowel Disease