• epithelium;
  • inflammation;
  • metagenomes;
  • microbiota;
  • mucosal immunity;
  • probiotics

The healthy human gut supports a complex and diverse microbiota, dominated by bacterial phylotypes belonging to Bacteroidetes and Firmicutes. In the inflamed gut, overall diversity decreases, coincident with a greater representation of Proteobacteria. There is growing evidence supporting an important role for human gut bacteria in mucosal immunity; interactions at the level of both intestinal and colonic epithelial cells, dendritic cells, and T and B immune cells have been documented. These interactions influence gut barrier and defense mechanisms that include antimicrobial peptide and secretory IgA synthesis. The functional effects of commensal bacteria on T helper cell differentiation have led to the emerging concept that microbiota composition determines T effector- and T regulatory-cell balance, immune responsiveness, and homeostasis. The importance of this biology in relation to immune homeostasis, inflammatory bowel disease, and the rising incidence of autoimmune diseases will be discussed. The detailed description of the human gut microbiota, integrated with evidence-based mechanisms of immune modulation, provides an exciting platform for the identification of next-generation probiotics and related pharmaceutical products.