Dramatic advances in molecular characterization of the largely noncultivable enteric microbiota have facilitated better understanding of the composition of this complex ecosystem at broad phylogenetic levels. This review outlines current understanding of mechanisms by which commensal bacteria are controlled and shaped into functional communities by innate and adaptive immune responses, antimicrobial peptides produced by epithelial cells and host genetic factors. Secretory IgA, which targets enteric bacteria, regulates the number, composition, and function of luminal bacteria. Likewise, epithelial production of antimicrobial peptides helps control enteric microbiota growth, translocation, and perhaps composition. The developing role of innate signaling pathways, such as Toll-like receptors and NOD2, is beginning to be studied, with dysbiosis following their genetic deletion. Inflammation and effector immune responses lead to decreased diversity and selective alterations of functionally active bacterial species such as Escherichia coli and Faecalibacterium prausnitzii that have proinflammatory and protective activities, respectively. Studies of humans, mice, and comparative species indicate that both genetic and early environmental factors influence the development of a stable intestinal microbiota. Genetic and mucosal immunity strongly influence the composition and function of enteric commensal bacteria. This understanding should help develop strategies to correct dysfunctional altered microbiota in genetically susceptible individuals, better diagnose and correct potential dysbiosis in high-risk individuals at a preclinical stage, and therapeutically target pathogenic bacterial species that help drive chronic inflammatory conditions.
