Enteric defensins are essential regulators of intestinal microbial ecology

Antimicrobial peptides are important effectors of innate immunity throughout the plant and animal kingdoms. In the mammalian small intestine, Paneth cell α-defensins are antimicrobial peptides that contribute to host defense against enteric pathogens. To determine if α-defensins also govern intestinal microbial ecology, we analyzed the intestinal microbiota in mice expressing a human α-defensin (DEFA5) and in mice lacking an enzyme required for processing of murine α-defensins. We detected significant α-defensin-dependent changes in microbiota composition, but not in total bacterial numbers, in these complementary models. Furthermore, DEFA5-expressing mice had striking losses of Segmented Filamentous Bacteria and fewer interleukin 17-producing lamina propria T cells. These data ascribe a new homeostatic role for α-defensins in regulating the makeup of the commensal microbiota.