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  3. A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage

A gut microbiota-bile acid axis promotes intestinal homeostasis upon aspirin-mediated damage

  • Cell Host Microbe. 2024 Jan 11:S1931-3128(23)00510-3. doi: 10.1016/j.chom.2023.12.015.
Ting Li 1,  Ning Ding 1,  Hanqing Guo 2,  Rui Hua 3,  Zehao Lin 3,  Huohuan Tian 3,  Yue Yu 3,  Daiming Fan 4,  Zuyi Yuan 5,  Frank J Gonzalez 6,  Yue Wu 7
Affiliations

Affiliations

  • 1 Department of Cardiovascular Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Molecular Cardiology, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China.
  • 2 Department of Gastroenterology, Xi'an Central Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 3 Department of Cardiovascular Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
  • 4 Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi, China.
  • 5 Department of Cardiovascular Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Molecular Cardiology, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China. Electronic address: zuyiyuan@mail.xjtu.edu.cn.
  • 6 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address: gonzalef@mail.nih.gov.
  • 7 Department of Cardiovascular Medicine, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China; Key Laboratory of Molecular Cardiology, Xi'an, Shaanxi, China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, Shaanxi, China. Electronic address: wu.yue@xjtu.edu.cn.
PMID: 38237593 DOI: 10.1016/j.chom.2023.12.015
Abstract

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.

Keywords

FXR; Wnt; aspirin; bile acid; gastrointestinal damage; gut microbiota; intestinal stem cells.

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