Gut Bacteroides ovatus ameliorates renal fibrosis by promoting the production of HDCA through upregulation of Clostridium scindens
Zi-lin Si, Hanyu Wang, Litao Wang, Yizhi Cao, Qing-Zhen Li, Kang Liu, Zhou Huang, Huiling Liu, Ya‐Jie Tan, Yin-yin Wang, Feng‐Qing Huang, Gao-Xiang Ma, Raphael N. Alolga, Miao Yan, Cheng Chen, Junhui Li, Jing Li, Hongwei Liu, Zhihao Zhang
Abstract
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.