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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 CX3CR1+ mononuclear phagocytes, including CX3CR1+ 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 CX3CR1+ 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 CX3CR1+ 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.

Microbiota interactions with host tissue support proper intestinal functions. In diseases such as inflammatory bowel disease, microbial shift along with epithelial dysfunctions are found. Understanding how intestinal epithelial functions are regulated by distinct commensal bacteria is key to improving outcomes in such diseases. Here, we identified a mouse commensal E. coli isolate, GDAR2-2, that promotes intestinal barrier repair in mouse colitis models including Citrobacter rodentium infection and dextran sulfate sodium-induced colitis. In mice, protection after GDAR2-2 colonization depends on CX3CR1+ mononuclear phagocytes (MNPs), which induce expansion of IL-22-secreting type 3 innate lymphoid cells. We detect upregulation of markers of transit amplifying cells, proliferation of which is downstream of IL-22 signaling. Protection is lost if IL-22 is blocked, indicating IL-22 driven epithelial regeneration is downstream of GDAR2-2 colonization. By co-culturing bone marrow derived macrophages with live GDAR2-2, we found GDAR2-2 promotes IL-1b production and the in vivo protection was lost after blockade of IL-1b. We further identified a subset of human commensal E. coli isolates that similarly induce CX3CR1+ MNP expansion and IL-1b mediated protection from C. rodentium infection in mice. This study reveals an unexpected role for IL-1b that promotes intestinal barrier repair and is induced by select commensal bacteria. Supported by NIH (AI125264, P30DK056338)

NGM agar recipe from wormbook

M9 Buffer recipe, transposed from the WormBook chapter: Maintenance ofC. elegans https://www.ncbi.nlm.nih.gov/books/NBK19649/

The gut microbiome is an important driver of host physiology and development. Altered abundance or membership of this microbe community can influence host health and disease progression, including the determination of host lifespan and healthspan. Here, we describe a robust pipeline to measure the microbiome abundance and composition in the C. elegans gut that can be applied to examine the role of the microbiome on host aging processes.