Gene-microbiota interactions contribute to the pathogenesis of inflammatory bowel disease

Genes and microbes converge in colitis Both host genetics and intestinal microbes probably contribute to a person's overall susceptibility to inflammatory bowel disease (IBD). The human gut microbe Bacteroides fragilis produces immunomodulatory molecules that it releases via outer membrane vesicles (OMVs). These molecules can protect mice from experimentally induced colitis. Chu et al. now find that OMV-mediated protection from colitis requires Atg16l1 and Nod2 genes whose human orthologs are associated with an increased risk for developing IBD. OMVs trigger an ATG16L1 and NOD2–dependent noncanonical autophagy pathway in dendritic cells (DCs). OMV-primed DCs, in turn, induce regulatory T cells in the intestine that protect against colitis. Science , this issue p. 1116