Gut Bacteroides ovatus ameliorates renal fibrosis by promoting the production of HDCA through upregulation of Clostridium scindens
Renal fibrosis, inflammation, and gut dysbiosis are all linked to chronic kidney disease (CKD). Here we show that Bacteroides ovatus protects against renal fibrosis. Mechanistically, B. ovatus enhances intestinal hyodeoxycholic acid (HDCA) levels by upregulating a strain of intestinal bacteria, Clostridium scindens, that has the capacity for direct HDCA production in mice. HDCA significantly promoted GLP-1 secretion by upregulating the expression of TGR5 and downregulating the expression of farnesoid X receptor (FXR) in the gut. Activation of renal GLP-1R attenuates renal fibrosis while delaying the subsequent development of CKD. In addition, HDCA can also protect against renal fibrosis by directly upregulating renal TGR5. The natural product neohesperidin (NHP) was found to exert its anti-renal fibrotic effects by promoting the growth of B. ovatus. Our findings provide mechanistic insights into the therapeutic potential of B. ovatus, C. scindens, and HDCA in treating CKD.
Authors
- Zhou Huang (ORCID: https://orcid.org/0000-0002-1255-1913)
- Hongwei Liu (ORCID: https://orcid.org/0000-0002-8200-8801)
- Yin-yin Wang
- Feng‐Qing Huang (ORCID: https://orcid.org/0000-0001-9185-9459)
- Zi-lin Si
- Qing-Zhen Li
- Raphael N. Alolga (ORCID: https://orcid.org/0000-0002-5714-4676)
- Jing Li (ORCID: https://orcid.org/0000-0001-9972-7397)
- Huiling Liu (ORCID: https://orcid.org/0000-0002-3662-9842)
- Junhui Li (ORCID: https://orcid.org/0000-0001-9862-2139)
- Kang Liu (ORCID: https://orcid.org/0000-0001-7929-6534)
- Cheng Chen (ORCID: https://orcid.org/0000-0002-4509-9273)
- Hanyu Wang (ORCID: https://orcid.org/0000-0002-6923-680X)
- Litao Wang (ORCID: https://orcid.org/0000-0003-2623-2961)
- Yan Miao (ORCID: https://orcid.org/0000-0003-2210-5658)
- Yizhi Cao (ORCID: https://orcid.org/0000-0001-6469-5962)
- Gao-Xiang Ma
- Ya-Jie Tan
- Zhihao Zhang
Institutions
- Tongji University (CN)
- China Pharmaceutical University (CN)
- Wuhan University (CN)
- Renmin Hospital of Wuhan University (CN)
- Central Hospital of Putuo District (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114830
- Citations
- 18
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 4.21