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Hvidovre Hospital - en del af Københavns Universitetshospital
Udgivet

Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts

Publikation: Bidrag til tidsskriftTidsskriftartikelpeer review

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  • Hyungjun Yang
  • Hengameh Chloé Mirsepasi-Lauridsen
  • Carsten Struve
  • Joannie M Allaire
  • Adeline Sivignon
  • Wayne Vogl
  • Else S Bosman
  • Caixia Ma
  • Abbas Fotovati
  • Gregor S Reid
  • Xiaoxia Li
  • Andreas Munk Petersen
  • Sébastien G Gouin
  • Nicolas Barnich
  • Kevan Jacobson
  • Hong Bing Yu
  • Karen Angeliki Krogfelt
  • Bruce A Vallance
Vis graf over relationer

Ulcerative colitis (UC) is a chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related to extra-intestinal pathogenic E. coli. These "pathobionts" exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of relevant animal models. Here, we established a mouse model using a representative UC pathobiont strain (p19A), and mice lacking single immunoglobulin and toll-interleukin 1 receptor domain (SIGIRR), a deficiency increasing susceptibility to gut infections. Strain p19A was found to adhere to the cecal mucosa of Sigirr -/- mice, causing modest inflammation. Moreover, it dramatically worsened dextran sodium sulfate-induced colitis. This potentiation was attenuated using a p19A strain lacking α-hemolysin genes, or when we targeted pathobiont adherence using a p19A strain lacking the adhesin FimH, or following treatment with FimH antagonists. Thus, UC pathobionts adhere to the intestinal mucosa, and worsen the course of colitis in susceptible hosts.

OriginalsprogEngelsk
TidsskriftGut Microbes
Vol/bind12
Udgave nummer1
Sider (fra-til)1847976
Antal sider19
ISSN1949-0976
DOI
StatusUdgivet - 1 dec. 2020

ID: 61405328