Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
Cell. 2020 Jul 23;182(2):447-462.e14. doi: 10.1016/j.cell.2020.05.048. Epub 2020 Jun 16.
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 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 in colonic mononuclear phagocytes, triggering inflammation. In parallel, periodontitis results in 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. When in the gut, Th17 cells of oral origin can be activated by translocated oral pathobionts and cause development of colitis, but they are not activated by gut-resident microbes. Thus, oral inflammation, such as periodontitis, exacerbates gut inflammation by supplying the gut with both colitogenic pathobionts and pathogenic T cells.
口腔感染导致口腔外疾病发病的确切机制尚不清楚。在这里，我们报告牙周炎在体内加重肠道炎症。牙周炎导致口腔条件致病菌（包括克雷伯氏菌和肠杆菌属物种）在口腔中扩张。聚集的口腔条件致病菌被摄入并转移到肠道，在那里它们激活结肠单核吞噬细胞中的炎症小体，引发炎症。与此同时，牙周炎导致口腔中产生口腔条件致病菌反应性 Th17 细胞。口腔条件致病菌反应性 Th17 细胞具有肠道趋向性，并迁移到发炎的肠道。当在肠道中时，源自口腔的 Th17 细胞可被转移的口腔条件致病菌激活，并导致结肠炎的发生，但它们不会被肠道常驻微生物激活。因此，口腔炎症（如牙周炎）通过向肠道提供致结肠炎的条件致病菌和致病性 T 细胞来加重肠道炎症。
