Large numbers of different bacterial species are resident in the lumen of the distal gastrointestinal tract. The normal intestinal host–microbial interactions are not well understood, but the relationship is generally believed to be either mutually beneficial or beneficial to one without disadvantage to the other. Animal model and clinical studies suggest that IBD (inflammatory bowel disease) may develop in a susceptible individual when the normal host–bacterial relationship is dysregulated. In addition to rodent models, this article reviews studies that have investigated the cellular and molecular mechanisms of interactions between intestinal mucosal cells and the resident luminal bacteria in healthy individuals and patients with ulcerative colitis and Crohn's disease. Mechanisms by which the intestinal mucosa is able to avoid pro-inflammatory responses to commensal bacteria (and their products) but able to respond appropriately to luminal pathogens is currently an area of active investigation. Such studies are beginning to provide important clues regarding possible alterations in the mucosa that lead to the development of pro-inflammatory responses to resident bacteria in patients with IBD. Approaches to alter the intestinal microflora for therapeutic purposes and their potential mechanisms of action are also discussed.

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