The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis

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.

Keywords: Klebsiella; TH17; colitis; dysbiosis; inflammasome; inflammatory bowel disease; microbiota; oral bacteria; pathobiont; periodontitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Colitis / microbiology
  • Colitis / pathology*
  • Colon / microbiology
  • Colon / pathology
  • Disease Models, Animal
  • Enterobacter / isolation & purification
  • Enterobacter / physiology*
  • Female
  • Gastrointestinal Microbiome*
  • Inflammasomes / metabolism
  • Interleukin-10 / deficiency
  • Interleukin-10 / genetics
  • Interleukin-1beta / metabolism
  • Klebsiella / isolation & purification
  • Klebsiella / physiology*
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mouth / microbiology*
  • Periodontitis / microbiology
  • Periodontitis / pathology
  • Th17 Cells / cytology
  • Th17 Cells / immunology
  • Th17 Cells / metabolism


  • Inflammasomes
  • Interleukin-1beta
  • Interleukin-10