Bile acid-induced metabolic changes in the colon promote Enterobacteriaceae expansion and associate with dysbiosis in Crohn's disease.

Autor: Holani R; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Bar-Yoseph H; Department of Gastroenterology, Rambam Health Care Campus, Haifa, Israel.; Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel., Krekhno Z; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Serapio-Palacios A; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Moon KM; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada., Stacey RG; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada., Donald KA; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Deng W; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada., Bressler B; Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada., Magaña AA; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada., Foster LJ; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada., Atser MG; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Johnson JD; Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Finlay B; Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.; Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.; Biochemistry and Molecular Biology Department, University of British Columbia, Vancouver, British Columbia, Canada.
Jazyk: angličtina
Zdroj: Science signaling [Sci Signal] 2024 Dec 17; Vol. 17 (867), pp. eadl1786. Date of Electronic Publication: 2024 Dec 17.
DOI: 10.1126/scisignal.adl1786
Abstrakt: Bile acids (BAs) affect the growth of potentially pathogenic commensals, including those from the Enterobacteriaceae family, which are frequently overrepresented in inflammatory bowel disease (IBD). BAs are normally reabsorbed in the ileum for recycling and are often increased in the colonic lumina of patients with IBD, including those with Crohn's disease (CD). Here, we investigated the influence of BAs on gut colonization by Enterobacteriaceae. We found increased abundance of Enterobacteriaceae in the colonic mucosae of patients with CD with a concomitant decrease in the transporters that resorb BAs in the ileum. The increase in Enterobacteriaceae colonization was greater in the colons of patients who had undergone terminal ileum resection compared with those with intact ileum, leading us to hypothesize that BAs promote intestinal colonization by Enterobacteriaceae. Exposure of human colonic epithelial cell lines to BAs reduced mitochondrial respiration, increased oxygen availability, and enhanced the epithelial adherence of several Enterobacteriaceae members. In a publicly available human dataset, mucosal Enterobacteriaceae was negatively associated with the expression of genes related to mitochondrial function. In a murine model, increased intestinal BA availability enhanced colonization by Escherichia coli in a manner that depended on bacterial respiration. Together, our findings demonstrate that BAs reduce mitochondrial respiration in the colon, leading to an increase in oxygen availability that facilitates Enterobacteriaceae colonization. This identification of BAs as facilitators of host-commensal interactions may be relevant to multiple intestinal diseases.
Databáze: MEDLINE