The intermucosal connection between the mouth and gut in commensal pathobiont-driven colitis

The precise mechanism by which oral infection contributes to the pathogenesis of extra-oral diseases remains unclear. Here, we report that periodontal inflammation exacerbates gut inflammation in vivo. Periodontitis leads to the expansion of oral pathobionts, including Klebsiella and Enterobacter species, in the oral cavity. Amassed oral pathobionts are ingested and translocate to the gut, where they activate the inflammasome, followed by robust IL-1beta production by colonic mononuclear phagocytes, thereby triggering inflammation. In parallel, periodontitis results in the generation of oral pathobiont-reactive Th17 cells in the oral cavity. Oral pathobiont-reactive Th17 cells are imprinted with gut tropism and migrate to the inflamed gut. Once in the gut, Th17 cells of oral origin can be activated by translocated oral pathobionts and cause the development of colitis, whereas they do not cross-react with gut-resident microbes. Thus, oral inflammation, such as periodontitis, exacerbates gut inflammation by supplying the gut with both pathogenic T cells and their reactive antigens.