Activation of a Specific Gut Bacteroides-Folate-Liver Axis Benefits for the Alleviation of Nonalcoholic Hepatic Steatosis
Shanshan Qiao,
Li Bao,
Kai Wang,
Shanshan Sun,
Mingfang Liao,
Chang Liu,
Nan Zhou,
Ke Ma,
Yuwei Zhang,
Yihua Chen,
Shuang-Jiang Liu,
Hongwei Liu
Affiliations
Shanshan Qiao
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Li Bao
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Kai Wang
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Shanshan Sun
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; School of Life Sciences, University of Science and Technology of China, No. 96 Jinzhai-Road, Hefei 230026, P. R. China
Mingfang Liao
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Chang Liu
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China
Nan Zhou
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China
Ke Ma
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China
Yuwei Zhang
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China
Yihua Chen
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China
Shuang-Jiang Liu
State Key Laboratory of Microbial Resources, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Corresponding author
Hongwei Liu
State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, No. 1 Beichenxi Road, Chaoyang District, Beijing 100101, P. R. China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing 100049, P. R. China; Corresponding author
Summary: A beneficial gut Bacteroides-folate-liver pathway regulating lipid metabolism is demonstrated. Oral administration of a Ganoderma meroterpene derivative (GMD) ameliorates nonalcoholic hepatic steatosis in the liver of fa/fa rats by reducing endotoxemia, enhancing lipid oxidation, decreasing de novo lipogenesis, and suppressing lipid export from the liver. An altered gut microbiota with an increase of butyrate and folate plays a causative role in the effects of GMD. The commensal bacteria Bacteroides xylanisolvens, Bacteroides thetaiotaomicron, Bacteroides dorei, and Bacteroides uniformis, which are enriched by GMD, are major contributors to the increased gut folate. Administration of live B. xylanisolvens reduces hepatic steatosis and enhances the folate-mediated signaling pathways in mice. Knockout of the folate biosynthetic folp gene in B. xylanisolvens blocks its folate production and beneficial effects. This work confirms the therapeutic potential of GMD and B. xylanisolvens in alleviating nonalcoholic hepatic steatosis and provides evidence for benefits of the gut Bacteroides-folate-liver pathway.
