| Abstract|| |
In recent years, novel insights have been gained into the role of bacterial microflora in health and disease. Commensal flora manipulation by probiotic bacteria has been investigated in human and experimental inflammatory bowel disease. Various probiotic species have shown promise in the treatment of ulcerative colitis, Crohn's disease and pouchitis in small studies, although a clear clinical benefit remains to be established.
Keywords: Crohn′s disease, inflammatory bowel disease, pouchitis, probiotics, ulcerative colitis
|How to cite this article:|
Almeghaiseeb ES. Probiotics: An overview and their role in inflammatory bowel disease. Saudi J Gastroenterol 2007;13:150-2
In the late 19 th century, microbiologists identified microflora in the gastrointestinal tracts (GITs) of healthy individuals that differed from those found in diseased individuals. The original observation of the positive role of these bacteria can be credited to the pioneering work of Metchnikoff in the early 1900s,  who suggested that these beneficial bacteria could be administered with a view to replacing harmful microbes with useful ones. The term "probiotic" meaning 'for life' was first coined in the 1960s by Lilly and Stillwell.  Probiotics were defined as microorganisms proven to exert health-promoting influences in humans and animals. Probiotics were recently redefined by an expert group to be 'live microorganisms which when administered in adequate amounts confer a health benefit on the host'. 
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|| |
Two main genera of Gram-positive bacteria, Lactobacillus and Bifidobacterium , are used extensively as probiotics.  However, while other probiotics such as Escherichia More Details , Enterococcus and Saccharomyces are also available in the market, their safety remains an area of concern. Recent evidence suggests that probiotic effects are strain-specific which means a beneficial effect produced by one strain cannot be assumed to be provided by another strain, even when it belongs to the same species.
| Possible Mechanism of Benefit|| |
Mechanisms for the benefits of probiotics are incompletely understood. However, three general benefits have been described:
- Suppression of growth or epithelial binding / invasion by pathogenic bacteria
- 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 factorβ (TGFβ) 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.
| Probiotics in IBD|| |
It has been suggested that gastrointestinal microflora are involved in the pathogenesis of inflammatory bowel diseases 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 treatment of ulcerative colitis in small studies although a clear clinical benefit remains to be established. Prevention of relapse is more thoroughly documented than the treatment of active disease. The following are illustrative controlled trials:
- E. coli 1917 Nissle was as effective as low-dose 5-aminosalicylic acid (5-ASA) in preventing relapse of ulcerative colitis in at least two controlled trials. 
- The combination of VSL#3 plus balsalazide was slightly more effective than balsalazide or mesalazine alone in a controlled trial of patients with acute mild-to-moderate ulcerative colitis. 
- The combination of a prebiotic (food intended to promote the growth of certain bacteria in the intestines) and a probiotic ( Bifidobacterium longum ) was associated with improvement in histologic scores and immune activation in a one-month randomized controlled trial. 
- Lactobacillus GG appeared to be more effective than standard treatment involving mesalazine in prolonging relapse-free time but did not influence relapse rates in patients with quiescent ulcerative colitis. 
- A product (BFM, Yakult Co. Ltd., Tokyo, Japan) containing B. breve , B. bifidum and L. acidophilus YIT N0168 has been evaluated as a dietary adjunct in the treatment of ulcerative colitis.  During the one-year 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 . 
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 Crohn's 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 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. 
- 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.  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.  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  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  and for prevention of onset of acute pouchitis during the first year after ileal pouch-anal anastomosis.  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-treated group.
- Treatment with VSL#3 was considered effective also in the prevention of acute pouchitis after surgery.  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 trials have suggested that at least one probiotic preparation (VSL#3) containing 5 x 10 per gram of four strains of Lactobacilli , three strains of Bifidobacteria and one strain of Streptococcus salivarius subspecies thermophilus may be effective in the prevention of pouchitis.
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Ebtissam S Almeghaiseeb
Division of Gastroenterology and Hepatology, Department of Medicine, Riyadh Military Hospital (B 90), PO Box 7897, Riyadh 11159
Source of Support: None, Conflict of Interest: None