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Commensal luminal bacteria stimulate protective or tolerogenic mucosal immune responses in normal (ie, resistant) hosts and detrimental responses, which result in chronic intestinal inflammation, in genetically susceptible hosts. Enteric pathogens appear to be important in the initiation and reactivation of human inflammatory bowel disease, and may be responsible for chronic inflammation in at least a subset of patients with inflammatory bowel diseases. Individual components of the commensal flora have variable abilities to induce inflammatory and protective immune responses; these preferential immune responses to individual bacterial species may be unique to each host's genetic background. Analogous to the balance between pro-and antiinflammatory cytokines and T-cell subsets, the ratio between protective (ie, probiotic) and aggressive commensal bacteria may determine whether there is mucosal homeostasis or chronic, relapsing intestinal inflammation. Therapeutic alteration of the luminal microenvironment by probiotic, prebiotic, and molecular strategies offers great promise for nontoxic treatment of inflammatory bowel disease.