The intestinal microbiota in inflammatory bowel diseases.

Abundant clinical and experimental evidence supports a role for resident microbiota in Crohn's disease and pouchitis, and probably in ulcerative colitis (UC). These disorders occur in areas of highest bacterial concentrations. Pouchitis and Crohn's colitis respond to antibiotics, while pouchitis and UC can be treated with probiotics. Serologic markers recognizing intestinal bacteria and yeast are present in the majority of Crohn's disease patients and may predict disease aggressiveness. Abnormal profiles of fecal and mucosally associated enteric bacteria (dysbiosis) occur in Crohn's disease, UC, pouchitis and experimental enterocolitis, with a proliferation of aggressive species that promote experimental colitis and a corresponding decrease in protective bacterial subsets. Many of these protective bacteria produce short-chain fatty acids, including butyrate, that promote epithelial barrier function, inhibit effector immune responses and induce regulatory T cell subsets. Furthermore, certain Clostridia species stimulate regulatory T cells that can inhibit intestinal inflammation. Animal models of chronic, immune-mediated enterocolitis convincingly demonstrate that enteric resident bacteria stimulate effector immune cells in susceptible hosts and that a subset of enteric bacteria has particularly aggressive activities, with host and bacterial specificity. Recent studies suggest parallel and perhaps complementary roles for enteric viruses, which have only very recently been identified.