It is widely known that the short chain fatty acid (SFA) butyrate, generated mainly through fermentation of dietary fibre by anaerobic bacteria, has beneficial effects on health. Less widely known is that butyrate, at the concentration (c20 mM) typically found in the healthy colonic lumen, is toxic to colon epithelial cells. It is probably the presence of the continuous adherent mucus layer in the healthy colon that ensures that butyrate concentrations in contact with the epithelium fall below the levels (c > 3 mM) that are consistently toxic in in vitro or ex vivo studies. In active ulcerative colitis, the adherent mucus layer is commonly weakened or absent. In this situation, it is likely that the luminal butyrate concentration will be toxic to the epithelium. It follows that butyrate at concentrations typically present in the colon lumen is probably beneficial when colitis is in remission but harmful when colitis has relapsed. This may explain the largely negative results of butyrate therapy in ulcerative colitis and could also account for the recently reported benefit from total enteral nutrition. It also suggests that butyrate should be regarded as a target for therapy in active ulcerative colitis rather than a solution.

In genetically susceptible individuals, an altered mucosal immune response against some commensal bacteria of the gut ecosystem appears to be the principal mechanism leading to intestinal lesions in inflammatory bowel disease (IBD). The information currently available does not provide an exact explanation about the origin of this important dysfunction of the interaction between host and commensal bacteria, but an altered microbial composition has been detected in the gut ecosystem of patients with Crohn's disease or ulcerative colitis. Prebiotics are food ingredients not digested nor absorbed in the upper intestinal tract that are fermented by intestinal bacteria in a selective way promoting changes in the gut ecosystem. Experimental and human studies have shown that inulin and oligofructose stimulate saccharolysis in the colonic lumen and favour the growth of indigenous lactobacilli and bifidobacteria. These effects are associated with reduced mucosal inflammation in animal models of IBD. Strong experimental evidence supports the hypothesis that inulin and oligofructose can offer an opportunity to prevent or mitigate intestinal inflammatory lesions in human Crohn's disease, ulcerative colitis, and pouchitis. Encouraging results have been obtained in preliminary clinical trials.

Human subjects and their enteric microbiota have evolved together to reach a state of mutual tolerance. Mounting evidence from both animal models and human studies suggests that inflammatory bowel disease (IBD) represents a malfunction of this relationship. The enteric microecology therefore represents an attractive therapeutic target with few side effects. Probiotics and prebiotics have been investigated in clinical trials as treatments for IBD, with conflicting results. The evidence for the use of probiotics in the management of pouchitis is persuasive and several studies indicate their effectiveness in ulcerative colitis. Trials of probiotics and prebiotics in Crohn's disease are less convincing. However, methodologies vary widely and a range of probiotic, prebiotic and combination (synbiotic) treatments have been tested in a variety of patient groups with an assortment of end points. Conclusions about any one treatment in a specific patient group can therefore only be drawn on evidence from relatively small numbers of patients. The present article reviews the role of the intestinal microbiota in the pathogenesis of IBD and addresses the clinical evidence for the therapeutic manipulation of bowel microbiota using probiotics, prebiotics and synbiotics in IBD.