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

Kitamoto, Sho ; Nagao-Kitamoto, Hiroko ; Jiao, Yizu ; Gillilland, Merritt G. ; Hayashi, Atsushi ; Imai, Jin ; Sugihara, Kohei ; Miyoshi, Mao ; Brazil, Jennifer C. ; Kuffa, Peter ; Hill, Brett D. ; Rizvi, Syed M. ; Wen, Fei ; Bishu, Shrinivas ; Inohara, Naohiro ; Eaton, Kathryn A. ; Nusrat, Asma ; Lei, Yu L. ; Giannobile, William V. ; Kamada, Nobuhiko

Cell, 2020-07, Vol.182 (2), p.447-462.e14 [Periódico revisado por pares]

United States: Elsevier Inc

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Título:
The Intermucosal Connection between the Mouth and Gut in Commensal Pathobiont-Driven Colitis
Autor: Kitamoto, Sho ; Nagao-Kitamoto, Hiroko ; Jiao, Yizu ; Gillilland, Merritt G. ; Hayashi, Atsushi ; Imai, Jin ; Sugihara, Kohei ; Miyoshi, Mao ; Brazil, Jennifer C. ; Kuffa, Peter ; Hill, Brett D. ; Rizvi, Syed M. ; Wen, Fei ; Bishu, Shrinivas ; Inohara, Naohiro ; Eaton, Kathryn A. ; Nusrat, Asma ; Lei, Yu L. ; Giannobile, William V. ; Kamada, Nobuhiko
Assuntos: Animals ; colitis ; Colitis - microbiology ; Colitis - pathology ; Colon - microbiology ; Colon - pathology ; Disease Models, Animal ; dysbiosis ; Enterobacter - isolation & purification ; Enterobacter - physiology ; Female ; Gastrointestinal Microbiome ; inflammasome ; Inflammasomes - metabolism ; inflammatory bowel disease ; Interleukin-10 - deficiency ; Interleukin-10 - genetics ; Interleukin-1beta - metabolism ; Klebsiella ; Klebsiella - isolation & purification ; Klebsiella - physiology ; Leukocytes, Mononuclear - cytology ; Leukocytes, Mononuclear - immunology ; Leukocytes, Mononuclear - metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; microbiota ; Mouth - microbiology ; oral bacteria ; pathobiont ; periodontitis ; Periodontitis - microbiology ; Periodontitis - pathology ; TH17 ; Th17 Cells - cytology ; Th17 Cells - immunology ; Th17 Cells - metabolism
É parte de: Cell, 2020-07, Vol.182 (2), p.447-462.e14
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
AUTHOR CONTRIBUTIONS
S.K. and N.K. conceived and designed the experiments. S.K. conducted most of the experiments with help from H.N.-K., A.H., M.M., J.I., K.S., P.K., and S.B. M.G.G. performed microbiome analysis. Y.J., N.I., and W.V.G. contributed to the establishment of the murine periodontitis model. J.C.B. and A.N. contributed to the establishment of the two-dimensional colonoid model. K.A.E. helped with GF animal experiments. B.D.H. and F.W. contributed the establishment of the CyTOF antibody panel. S.M.R. and Y.L.L. conducted the CyTOF analysis. S.K. and N.K. analyzed the data. S.K. and N.K. wrote the manuscript with contributions from all authors.
Descrição: 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. [Display omitted] •Oral inflammation triggers expansion of oral pathobionts•Ectopic gut colonization by oral pathobionts promotes colitis through IL-1β•Oral Th17 cells that arise during oral inflammation can migrate to the gut•Oral pathobiont-reactive Th17 cells that migrate to the gut contribute to colitis Periodontitis leads to expansion of pathobiont members of the oral microbiota, which promote colitis via colonization of the gut as well as induction of migratory Th17 cells, constituting a dual microbiome and immune mechanism linking oral and gut health.
Editor: United States: Elsevier Inc
Idioma: Inglês

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

United States: Elsevier Inc

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