Gut microbiota and intestinal FXR mediate the clinical benefits of metformin

• Published in: Nature medicine Vol. 24; no. 12; pp. 1919 - 1929
• Main Authors: Sun, Lulu, Xie, Cen, Wang, Guang, Wu, Yue, Wu, Qing, Wang, Xuemei, Liu, Jia, Deng, Yangyang, Xia, Jialin, Chen, Bo, Zhang, Songyang, Yun, Chuyu, Lian, Guan, Zhang, Xiujuan, Zhang, Heng, Bisson, William H, Shi, Jingmin, Gao, Xiaoxia, Ge, Pupu, Liu, Cuihua, Krausz, Kristopher W, Nichols, Robert G, Cai, Jingwei, Rimal, Bipin, Patterson, Andrew D, Wang, Xian, Gonzalez, Frank J, Jiang, Changtao
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.12.2018
• Subjects: Antidiabetics; Bacteroides - drug effects; Bacteroides - pathogenicity; Bile Acids and Salts - metabolism; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - genetics; Diabetes Mellitus, Type 2 - microbiology; Diabetes Mellitus, Type 2 - pathology; Diet, High-Fat - adverse effects; Digestive system; Gastrointestinal Microbiome - drug effects; Gastrointestinal Microbiome - genetics; Gastrointestinal tract; Gene Expression Regulation, Bacterial - drug effects; Gluconeogenesis; Glucose; Glucose Intolerance - drug therapy; Glucose Intolerance - genetics; Glucose Intolerance - microbiology; Glucose tolerance; Hepatocytes; High fat diet; Humans; Hyperglycemia; Hyperglycemia - drug therapy; Hyperglycemia - genetics; Hyperglycemia - microbiology; Hyperglycemia - pathology; Intestinal microflora; Intestine; Intolerance; Metabolism; Metabolites; Metabolome - drug effects; Metabolome - genetics; Metabolomics; Metagenomics - methods; Metformin; Metformin - administration & dosage; Mice; Microbiota; Microorganisms; Obesity - drug therapy; Obesity - genetics; Obesity - microbiology; Obesity - pathology; Receptors, Cytoplasmic and Nuclear - genetics; Signaling; Ursodeoxycholic Acid - analogs & derivatives
• ISSN: 1078-8956; 1546-170X
• DOI: 10.1038/s41591-018-0222-4

The anti-hyperglycemic effect of metformin is believed to be caused by its direct action on signaling processes in hepatocytes, leading to lower hepatic gluconeogenesis. Recently, metformin was reported to alter the gut microbiota community in humans, suggesting that the hyperglycemia-lowering actio...