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

Hyungjun Yang (1) , Hengameh Chloé Mirsepasi-Lauridsen (2, 3) , Carsten Struve (2) , Joannie M Allaire (1) , Adeline Sivignon (4) , Wayne Vogl (5) , Else S Bosman (1) , Caixia Ma (1) , Abbas Fotovati (1) , Gregor S Reid (1) , Xiaoxia Li (6) , Andreas Munk Petersen (7) , Sébastien Gouin (8) , Nicolas Barnich (4) , Kevan Jacobson (1) , Hong Bing Yu (1) , Karen Angeliki Krogfelt (2) , Bruce A Vallance (1)

1 BCCHR - BC Children's Hospital Research Institute [Vancouver, BC, Canada]
2 Statens Serum Institut [Copenhagen]
3 Department of Biology [Copenhagen]
4 M2iSH - Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte
5 UBC - University of British Columbia
6 Department of Immunology [Lerner Research Institute, Cleveland Clinic]
7 Copenhagen University Hospital
8 CEISAM - Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation

Ulcerative colitis (UC) is chronic inflammatory condition linked to intestinal microbial dysbiosis, including the expansion of E. coli strains related to extra-intestinal E. coli. These “pathobionts” exhibit pathogenic properties, but their potential to promote UC is unclear due to the lack of suitable 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. p19A was found to adhere to the cecal mucosa of Sigirr−/− mice, causing modest inflammation. Moreover, it dramatically worsened DSS induced colitis, in concert with adherence to, and penetration of the inflamed mucosa. This pathogenicity was lost in a p19A strain lacking the adhesin FimH; following treatment with FimH antagonists, or was attenuated when using a p19A strain lacking a-hemolysin genes. Thus UC pathobionts can worsen the course of colitis in susceptible hosts.

Mots clés: intestinal microbiota; Crohn’s disease; ulcerative colitis; inflammatory bowel disease; in vivo mouse model

Domaines: Maladies infectieuses; Hépatologie et Gastroentérologie; Bactériologie

Hyungjun Yang, Hengameh Chloé Mirsepasi-Lauridsen, Carsten Struve, Joannie M Allaire, Adeline Sivignon, et al.. Ulcerative Colitis-associated E. coli pathobionts potentiate colitis in susceptible hosts. Journal of Immunology, 2020, 12 (1), pp.1-20. ⟨10.1080/19490976.2020.1847976⟩. ⟨hal-03003143⟩