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Probiotics: An overview and their role in inflammatory bowel disease Presented by Dr. Nazia Haque MPhil(2nd part student) Department of microbiology, MMC NEW HORIZON Year : 2007 | Volume : 13 | Issue : 3 | Page : 150-152 Introduction • 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'. • Simplified definition of Probiotics as “live, nonpathogenic bacteria that may be effective in the treatment or prevention of certain human diseases”. For example• The oral administration of live Lactobacillus rhamnosus strain GG significantly reduce the number of cases of nosocomial diarrhoea in young children. Beneficial effect of Probiotic Possible beneficial effect are – • Either in providing colonization resistance by which the non-pathogen excludes the pathogen from binding sites on the mucosa or • Enhancing the immune response against the pathogen or • In reducing the inflammatory response against the pathogen. Commonly Used Probiotic Organisms • Two main genera of GP bacteria(Lactobacillus & Bifidobacterium) are used extensively as probiotics. • Other probiotics such as Escherichia , Enterococcus & Saccharomyces are also available in the market. • 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 Mechanisms of Benefit • Mechanisms for the benefits of probiotics are incompletely understood. However, three general benefits have been described: 1. Suppression of growth or epithelial binding/invasion by pathogenic bacteria 2. Improvement of intestinal barrier function 3. Modulation of the immune system. Theories exist regarding probiotic preparations: Several theories exist regarding probiotic preparations. These include: • Stimulation of protective cytokines including IL-10 and TGFβ. • Suppression of pro-inflammatory cytokines such as TNF in the mucosa of patients with pouchitis and Crohn's disease. • Limit the migration of TH1 cells in inflammed colon tissue in inflammatory bowel disease (IBD). Role of Probiotics in IBD • It has been suggested that GI microflora are involved in the pathogenesis of inflammatory bowel diseases in genetically susceptible subjects. • 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 was as effective as low-dose 5-aminosalicylic acid (5-ASA) in preventing relapse of ulcerative colitis. • The combination of VSL#3 plus balsalazide was slightly more effective than balsalazide or mesalazine alone in 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) was associated with improvement in histologic scores and immune activation in a one-month randomized controlled trial. • Lactobacillus more effective than standard treatment in patients with quiescent ulcerative colitis. • A product containing B. breve , B. bifidum and L. acidophilus 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 doubleblind 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. Some of the more important studies: • Preventive effect of Lactobacillus on the appearance of recurrent lesions of CD after surgery. • A combination of three Bifidobacterium species, four Lactobacillus species and S.salivarius ssp. has been evaluated 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. • 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. • 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. 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. • Probiotic was inefficient as primary therapy for the clinical improvement of pouch inflammation. • 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 • 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.