Aspirin-related gastrointestinal damage is of growing concern. Aspirin use modulates the gut microbiota and associated metabolites, such as bile acids (BAs), but how this impacts intestinal homeostasis remains unclear. Herein, using clinical cohorts and aspirin-treated mice, we identified an intestinal microbe, Parabacteroides goldsteinii, whose growth is suppressed by aspirin. Mice supplemented with P. goldsteinii or its BA metabolite, 7-keto-lithocholic acid (7-keto-LCA), showed reduced aspirin-mediated damage of the intestinal niche and gut barrier, effects that were lost with a P. goldsteinii hdhA mutant unable to generate 7-keto-LCA. Specifically, 7-keto-LCA promotes repair of the intestinal epithelium by suppressing signaling by the intestinal BA receptor, farnesoid X receptor (FXR). 7-Keto-LCA was confirmed to be an FXR antagonist that facilitates Wnt signaling and thus self-renewal of intestinal stem cells. These results reveal the impact of oral aspirin on the gut microbiota and intestinal BA metabolism that in turn modulates gastrointestinal homeostasis.

阿司匹林相关的胃肠道损害日益受到关注。阿司匹林的使用可调节肠道微生物群和相关代谢物，例如胆汁酸（BA），但这如何影响肠道稳态仍不清楚。在此，通过临床队列和阿司匹林治疗的小鼠，我们鉴定了一种肠道微生物，金氏副杆菌，其生长被阿司匹林抑制。补充金石假单胞菌或其 BA 代谢物 7-酮石胆酸 (7-keto-LCA) 的小鼠表现出阿司匹林介导的肠道生态位和肠道屏障损伤减少，而金石假单胞菌 hdhA 突变体则失去了这种作用无法生成 7-keto-LCA。具体来说，7-酮-LCA 通过抑制肠道 BA 受体、法尼醇 X 受体 (FXR) 的信号传导来促进肠上皮的修复。7-Keto-LCA 被证实是一种 FXR 拮抗剂，可促进 Wnt 信号传导，从而促进肠道干细胞的自我更新。这些结果揭示了口服阿司匹林对肠道微生物群和肠道 BA 代谢的影响，进而调节胃肠道稳态。