The role of gut microbiota in intestinal immune tolerance

The intestinal mucosa is constantly exposed to foreign substances and thus owns several lines of defense machinery, including epithelial barrier and secretory IgA to prevent the invasion of pathogens. Meanwhile, the intestinal immune system elicits immune tolerance to food antigens and commensal bacteria. Dysregulation of the intestinal immunity often causes severe inflammatory disorders such as inflammatory bowel disease, allergies, and autoimmune diseases. Regulatory T（Treg） cells, one of the major T cell subsets in the intestine, play a critical role in maintaining immune homeostasis. Compelling evidence has demonstrated that commensal bacteria in the intestine are essential for the expansion of Treg cells in the intestinal lamina propria. This effect is at least partly mediated by metabolites like butyrate produced by commensal bacteria. Bacterial metabolites are transported to the bloodstream to affect the immune response in local and systemic tissues, especially in the respiratory system. Thus, the regulation of immune response by gut microbiota and its pathological relevance has drawn much attention. Furthermore, the development of therapies targeting the gut microbiota by fecal transplantation and probiotic administration is underway. This article will review the latest findings on the immune regulation by commensal bacteria and discuss therapeutic intervention strategies targeting the intestinal microbiota.