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169]
New Horizon
Probiotics: An Overview and their Role in Inflammatory
Bowel Disease
Ebtissam S. Almeghaiseeb

Division of
Gastroenterology and
ABSTRACT
Hepatology, Department of In recent years, novel insights have been gained into the role of bacterial microflora in health and disease.
Medicine, Riyadh Military

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Commensal flora manipulation by probiotic bacteria has been investigated in human and experimental
Hospital, Riyadh, inflammatory bowel disease. Various probiotic species have shown promise in the treatment of ulcerative colitis,
Saudi Arabia Crohns disease and pouchitis in small studies, although a clear clinical benefit remains to be established.

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Address:

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Ebtissam S. Almeghaiseeb, Key Words: Crohns disease, inflammatory bowel disease, pouchitis, probiotics, ulcerative colitis
Division of

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Gastroenterology and Received 29.05.2007, Accepted 19.06.2007

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Hepatology, Department of The Saudi Journal of Gastroenterology 2007 13(3):150-52
Medicine, Riyadh Military

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Hospital (B 90), PO Box
7897, Riyadh 11159, kn kno ee
Saudi Arabia.
E-mail:
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e_meghaiseeb@yahoo.com
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In the late 19th century, microbiologists identified microflora market, their safety remains an area of concern. Recent
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in the gastrointestinal tracts (GITs) of healthy individuals evidence suggests that probiotic effects are strain-specific
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that differed from those found in diseased individuals. The which means a beneficial effect produced by one strain
original observation of the positive role of these bacteria cannot be assumed to be provided by another strain, even
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can be credited to the pioneering work of Metchnikoff when it belongs to the same species.
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in the early 1900s,[1] who suggested that these beneficial

POSSIBLE MECHANISM OF BENEFIT
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bacteria could be administered with a view to replacing

harmful microbes with useful ones. The term probiotic
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meaning for life was first coined in the 1960s by Lilly and Mechanisms for the benefits of probiotics are incompletely
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Stillwell.[2] Probiotics were defined as microorganisms proven understood. However, three general benefits have been
to exert health-promoting influences in humans and animals. described:
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Probiotics were recently redefined by an expert group to be Suppression of growth or epithelial binding / invasion by
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live microorganisms which when administered in adequate pathogenic bacteria

amounts confer a health benefit on the host.[3]
In recent years, there has been an upsurge in research in
probiotics as well as growing commercial interest in the
probiotic food concept. This increased research has resulted
in significant advances in our understanding and ability to
characterize specific probiotic organisms, which has resulted
in an increasing amount of evidence indicating health
benefits by consumption of food containing probiotics.
COMMONLY USED PROBIOTIC ORGANISMS
Improvement of intestinal barrier function
Modulation of the immune system. Several theories
exist regarding probiotic preparations. These include
stimulation of protective cytokines including interleukin
(IL)-10 and transforming growth factor (TGF) and
suppression of pro-inflammatory cytokines such as
tumor necrosis factor (TNF) in the mucosa of patients
with pouchitis and Crohn's disease (CD). Saccharomyces
boulardii may limit the migration of T-helper 1 (TH1)
cells in inflamed colon tissue in inflammatory bowel
disease (IBD) in experimental studies.

Two main genera of Gram-positive bacteria, Lactobacillus PROBIOTICS IN IBD

and Bifidobacterium, are used extensively as probiotics.[3]
However, while other probiotics such as Escherichia, It has been suggested that gastrointestinal microflora are
Enterococcus and Saccharomyces are also available in the involved in the pathogenesis of inflammatory bowel diseases

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in genetically susceptible subjects with immunological
dysregulation. In support of this hypothesis is the observation
that there is an increase in the number of microorganisms
and a change in the various populations of normal flora
in IBD patients. Interactions between the commensal
microflora and the intestinal mucosa stimulate inflammatory
activity.
PROBIOTICS IN ULCERATIVE COLITIS
Various probiotic species have shown promise in the
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treatment of ulcerative colitis in small studies although a
clear clinical benefit remains to be established. Prevention of
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relapse is more thoroughly documented than the treatment
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of active disease. The following are illustrative controlled
trials:
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E. coli 1917 Nissle was as effective as low-dose 5-
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aminosalicylic acid (5-ASA) in preventing relapse of
ulcerative colitis in at least two controlled trials.[4]
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The combination of VSL#3 plus balsalazide was slightly
more effective than balsalazide or mesalazine alone in a
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controlled trial of patients with acute mild-to-moderate
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ulcerative colitis.[5]
The combination of a prebiotic (food intended to
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promote the growth of certain bacteria in the intestines)
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and a probiotic (Bifidobacterium longum) was associated
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with improvement in histologic scores and immune
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activation in a one-month randomized controlled
trial.[6]
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Lactobacillus GG appeared to be more effective than
standard treatment involving mesalazine in prolonging
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relapse-free time but did not influence relapse rates in
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patients with quiescent ulcerative colitis.[7]
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A product (BFM, Yakult Co. Ltd., Tokyo, Japan)
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containing B. breve, B. bifidum and L. acidophilus YIT
N0168 has been evaluated as a dietary adjunct in the
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treatment of ulcerative colitis.[8] During the one-year
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duration of the study, exacerbation of symptoms occurred
in three of 11 patients in the supplemented group and
in nine of ten patients in the placebo group but no
difference was seen in the colonoscopic findings.
The study by Kruis et al. was performed in a double-blind
fashion in 103 patients for 12 weeks. Relapse rates were
11% for mesalazine and 16% for E. coli.[9]
In conclusion: The benefits of probiotics for maintenance
therapy in ulcerative colitis are still regarded as weak evidence
since the effect is comparable with placebo.
PROBIOTICS IN CROHNS DISEASE
Probiotics are being investigated actively in the management
of CD. Below are some of the more important studies:
A placebo-controlled study has been performed in order
Probiotics
to evaluate the preventive effect of Lactobacillus GG on
the appearance of recurrent lesions of CD after surgery. At
the end of one year, there were no statistically significant
differences between the patients regarding endoscopic
recurrence or severity of recurrent lesions.[10]
A combination of three Bifidobacterium species, four
Lactobacillus species and S. salivarius ssp. thermophilus
(VSL#3, VSL Pharmaceuticals) has been evaluated
in a single- blind study for the prevention of recurrent
inflammation after surgery. [11] The patients either
received a nonabsorbable antibiotic (rifaximin) for three
months followed by nine months intake of the probiotic
or mesalazine for 12 months. After one year, there was a
significantly lower rate of severe endoscopic recurrence
in patients treated with the antibiotic and probiotic
combination.
Patients with active colonic CD were treated with
prednisolone on a standard schedule and were also
randomized to receive E. coli (Nissle 1917) or placebo for
one year.[12] Patients in the two groups had similar rates
of remission but patients treated with prednisolone and
E. coli had fewer relapses than patients in the placebo
group.
In conclusion: The effect of probiotics in CD is still unclear.
Several studies done in this area failed to prove an established
benefit. The reasons for the heterogeneity could be due to
several factors such as the specific probiotics (and doses)
used, differences in study duration, characteristics of the
included patients (e.g., location of disease) and endpoints
that were measured.
PROBIOTICS AND POUCHITIS
Pouchitis is a nonspecific inflammation of the ileal reservoir
after ileal-anal anastomosis for ulcerative colitis. Disturbances
in the intestinal micro flora may be the triggering factor in
its pathogenesis.
Patients with endoscopic and histological signs of
inflammation of the pouch mucosa were included in a
double-blind study on the effects of Lactobacillus GG[13]
but the probiotic was inefficient as primary therapy for
the clinical improvement of pouch inflammation.
The probiotic preparation VSL#3 has been evaluated for
efficacy in maintaining remission of pouchitis[14] and for
prevention of onset of acute pouchitis during the first
year after ileal pouch-anal anastomosis.[15] All subjects
in the placebo group of the first study had relapses
whilst 85% of patients (17 of 20) treated with VSL#3
were still in remission after nine months. Similar results
were obtained in the second study where remission was
maintained at one year in one patient in the placebo
group (one of 16) and in 17 of 20 patients in the VSL#3-
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Almeghaiseeb

treated group. et al. Synbiotic therapy (Bifidobacterium longum/Synergy 1) initiates

Treatment with VSL#3 was considered effective also in
the prevention of acute pouchitis after surgery.[16] Eight
out of 20 patients treated with placebo and two of 20
treated with the probiotic product had an episode of
acute pouchitis within one year.
CONCLUSION
Literature on the role of probiotics in the treatment of
pouchitis is still regarded as limited although small controlled
resolution of inflammation in patients with active ulcerative colitis: A
randomized controlled pilot trial. Gut 2005;54:242-9.
7. Zocco MA, dal Verme LZ, Cremonini F, Piscaglia AC, Nista EC, Candelli M,
et al. Efficacy of lactobacillus GG in maintaining remission of ulcerative
colitis. Aliment Pharmacol Ther 2006;23:1567-74.
8. Ishikawa H, Akedo I, Umesaki Y, Tanaka R, Imaoka A, Otani T.
Randomized controlled trial of the effect of bifidobacteria-fermented
milk on ulcerative colitis. J Am Coll Nutr 2003;22:56-63.
9. Kruis W, Schutz E, Fric P, Fixa B, Judmaier G, Stolte M. Double-blind
comparison of an oral Escherichia coli preparation and mesalazine in
maintaining remission of ulcerative colitis. Aliment Pharmacol Ther

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1997;11:853-8.
trials have suggested that at least one probiotic preparation 10. Prantera C, Scribano ML, Falasco G andreoli A, Luzi C. Ineffectiveness
(VSL#3) containing 5 x 10 per gram of four strains of of probiotics in preventing recurrence after curative resection for

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Lactobacilli, three strains of Bifidobacteria and one strain Crohns disease: A randomized controlled trial with Lactobacillus GG.

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of Streptococcus salivarius subspecies thermophilus may be Gut 2002;51:405-9.
effective in the prevention of pouchitis. 11. Gionchetti P, Amadini C, Rizzello F, Venturi A, Poggioli G, Campieri M.

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Probiotics for the treatment of postoperative complications following

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intestinal surgery. Best Pract Res Clin Gastroenterol 2003;17:821-31.
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3. FAO/WHO. Evaluation of health and nutritional properties of probiotics G, et al. Oral bacteriotherapy as maintenance treatment in patients
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Organization of the United Nations and World Health Organization, 15. Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, et
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et al. Prophylaxis of pouchitis onset with probiotic therapy: A double-

5. Tursi A, Brandimarte G, Giorgetti GM, Forti G, Modeo ME, Gigliobianco blind, placebo-controlled trial. Gastroenterology 2003;124:1202-9.
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A. Low-dose balsalazide plus a high-potency probiotic preparation is

more effective than balsalazide alone or mesalazine in the treatment
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of acute mild-to-moderate ulcerative colitis. Med Sci Monit 2004;10:

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I126-31. Source of Support: Nil, Conflict of Interest: None declared.

6. Furrie E, Macfarlane S, Kennedy A, Cummings JH, Walsh SV, Oneil DA,
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