The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice

Wei Zhou, Wen-hui Wu, Zi-lin Si, Hui-ling Liu, Hanyu Wang, Hong Jiang, Ya-fang Liu, Raphael N. Alolga, Cheng Chen, Shi-jia Liu, Xue-yan Bian, Jin-jun Shan, Jing Li, Ning-hua Tan () and Zhi-hao Zhang ()
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Wei Zhou: China Pharmaceutical University
Wen-hui Wu: China Pharmaceutical University
Zi-lin Si: China Pharmaceutical University
Hui-ling Liu: China Pharmaceutical University
Hanyu Wang: China Pharmaceutical University
Hong Jiang: China Pharmaceutical University
Ya-fang Liu: China Pharmaceutical University
Raphael N. Alolga: China Pharmaceutical University
Cheng Chen: Renmin Hospital of Wuhan University
Shi-jia Liu: Affiliated Hospital of Nanjing University of Chinese Medicine
Xue-yan Bian: Ningbo Hospital of Zhejiang University
Jin-jun Shan: Nanjing University of Chinese Medicine
Jing Li: China Pharmaceutical University
Ning-hua Tan: China Pharmaceutical University
Zhi-hao Zhang: China Pharmaceutical University

Nature Communications, 2022, vol. 13, issue 1, 1-19

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41467-022-33824-6

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