The microbiota in IBD

One of the driving factors for the resurgence of interest in the gut microbiota has been the discovery that several genetic risk factors for Crohn's disease and ulcerative colitis code for proteins that sense or regulate the host response to the microenvironment. There is also extensive experimental evidence for the role of the microbiota in the pathogenesis of these disorders. Curiously, most current therapeutic strategies for inflammatory bowel disease (IBD) are directed toward suppression or modulation of the host immunoinflammatory response with little attention to manipulating host-microbe interactions. In addition to loss of diversity, there are individual microbial alterations in Crohn's disease and ulcerative colitis and colitis-associated cancer. The challenges for therapeutic manipulation of the microbiota in such patients are considerable and include the marked heterogeneity of each disorder. This is reflected in heterogeneity of therapeutic responsiveness, an example of which is the variable efficacy of antibiotics depending on the disease phenotype. Several research groups have reported the efficacy with pre- and/or probiotics in different animal models of IBD and in some cases with convincing mechanistic data including the immunomodulatory effects of some but not all probiotics. Notwithstanding, results in humans have been contradictory or disappointing. Attention has, therefore, moved toward unresolved issues such as probiotic strain selection, product quality, dose, and timing of delivery. In contrast to IBD, a role for disturbed host-microbe interactions has received little attention in IBS, but deserves consideration with the identification of post-infectious IBS as a distinct entity. In further contrast to human IBD, controlled trials have shown that some but not all probiotics have significant therapeutic efficacy in IBS. In addition to improved strain selection and the need to move from microbes to mechanisms, a requirement for further progress is the pursuit of new biomarkers.