Interleukin-1β secretion induced by mucosa-associated gut commensal bacteria promotes intestinal barrier repair

The gut microbiota is essential for maintenance and repair of the intestinal epithelial barrier. As shifts in both intestinal epithelial barrier function and microbiota composition are found in inflammatory bowel disease patients, it is critical to understand the role of distinct bacteria in regulating barrier repair. We identified a mouse commensal E. coli isolate, GDAR2-2, that protects mice from Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. Colonization with GDAR2-2 in mice resulted in expansion of CX(3)CR1(+) mononuclear phagocytes, including CX(3)CR1(+) macrophages/dendritic cells and monocytes, along with IL-22-secreting type 3 innate lymphoid cells and improved epithelial barrier function. In vitro co-culture of macrophages with GDAR2-2 resulted in IL-1β production. In vivo, protection after GDAR2-2 colonization was lost after depletion of CX(3)CR1(+) MNPs, or blockade of IL-1β or IL-22. We further identified human commensal E. coli isolates that similarly protect mice from C. rodentium infection through CX(3)CR1(+) MNP and IL-1β production. Together, these findings demonstrate an unexpected role for commensal bacteria in promoting IL-1β secretion to support intestinal barrier repair.