Title: The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis
Author: Sho Kitamoto, Hiroko Nagao-Kitamoto, Yizu Jiao, Merritt G. Gillilland, Atsushi Hayashi, Jin Imai, Kohei Sugihara, Mao Miyoshi, Jennifer C. Brazil, Peter Kuffa, Brett D. Hill, Syed M. Rizvi, Fei Wen, Shrinivas Bishu, Naohiro Inohara, Kathryn A. Eaton, Asma Nusrat, Yu L. Lei, William V. Giannobile, Nobuhiko Kamada
Abstract: The precise mechanism by which oral infection contributes to the pathogenesis of extra-oraldiseases remains unclear. Here, we report that periodontal inflammation exacerbatesgut inflammation in vivo. Periodontitis leads to expansion of oral pathobionts, including Klebsiella and Enterobacter species, in the oral cavity. Amassed oral pathobionts are ingested and translocateto the gut, where they activate the inflammasome in colonic mononuclear phagocytes,triggering inflammation. In parallel, periodontitis results in generation of oralpathobiont-reactive Th17 cells in the oral cavity. Oral pathobiont-reactive Th17 cellsare imprinted with gut tropism and migrate to the inflamed gut. When in the gut, Th17cells of oral origin can be activated by translocated oral pathobionts and cause developmentof colitis, but they are not activated by gut-resident microbes. Thus, oral inflammation,such as periodontitis, exacerbates gut inflammation by supplying the gut with bothcolitogenic pathobionts and pathogenic T cells.