2. Academic Validation
  3. The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice

The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice

  • Nat Commun. 2022 Oct 14;13(1):6081. doi: 10.1038/s41467-022-33824-6.
Wei Zhou # 1,  Wen-Hui Wu # 1,  Zi-Lin Si # 1,  Hui-Ling Liu 1,  Hanyu Wang 1,  Hong Jiang 1,  Ya-Fang Liu 1,  Raphael N Alolga 1,  Cheng Chen 2,  Shi-Jia Liu 3,  Xue-Yan Bian 4,  Jin-Jun Shan 5,  Jing Li 6,  Ning-Hua Tan 7,  Zhi-Hao Zhang 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
  • 2 Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China.
  • 3 Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.
  • 4 Ningbo Hospital of Zhejiang University, Ningbo, China.
  • 5 Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing, China.
  • 6 School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
  • 7 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. [email protected].
  • 8 State Key Laboratory of Natural Medicines, Department of TCMs Pharmaceuticals, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China. [email protected].
  • # Contributed equally.
PMID: 36241632 DOI: 10.1038/s41467-022-33824-6
Abstract

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

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