Holani Ravi, Bar-Yoseph Haggai, Krekhno Zakhar, Serapio-Palacios Antonio, Moon Kyung-Mee, Stacey Richard G, Donald Katherine A, Deng Wanyin, Bressler Brian, Magaña Armando A, Foster Leonard J, Atser Michael G, Johnson James D, Finlay Barton
Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
Sci Signal. 2024 Dec 17;17(867):eadl1786. doi: 10.1126/scisignal.adl1786.
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 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.
胆汁酸（BAs）会影响潜在致病性共生菌的生长，包括肠杆菌科的细菌，这些细菌在炎症性肠病（IBD）中常常过度增殖。胆汁酸通常在回肠被重吸收以进行循环利用，而在IBD患者（包括克罗恩病（CD）患者）的结肠腔中，胆汁酸含量常常升高。在此，我们研究了胆汁酸对肠杆菌科细菌在肠道定殖的影响。我们发现，CD患者结肠黏膜中肠杆菌科细菌丰度增加，同时回肠中重吸收胆汁酸的转运蛋白减少。与回肠完整的患者相比，接受回肠末端切除的患者结肠中肠杆菌科细菌定殖的增加更为明显，这使我们推测胆汁酸会促进肠杆菌科细菌在肠道的定殖。将人结肠上皮细胞系暴露于胆汁酸会降低线粒体呼吸作用、增加氧的可利用性，并增强几种肠杆菌科细菌成员与上皮细胞的黏附。在一个公开的人类数据集中，黏膜中的肠杆菌科细菌与线粒体功能相关基因的表达呈负相关。在一个小鼠模型中，肠道胆汁酸可利用性的增加以依赖细菌呼吸的方式增强了[具体细菌名称未给出]的定殖。总之，我们的研究结果表明，胆汁酸会降低结肠中的线粒体呼吸作用，导致氧可利用性增加，从而促进肠杆菌科细菌的定殖。胆汁酸作为宿主与共生菌相互作用促进因子的这一发现可能与多种肠道疾病相关。
