Dihydromyricetin from Vine Tea ( Ampelopsis grossedentata ) Prevents Diet-Induced Obesity by Modulating the Gut Microbiota Composition

Background: Gut microbiota plays a decisive role in the pathogenesis of obesity. Targeting the gut microbiota are potential therapies for obesity. Dihydromyricetin (DMY), a flavanonol compound isolated from vine tea (Ampelopsis grossedentata) in the traditional Chinese medicine, improves glucose and lipid metabolism despite of low bioavailability. Methods: Mice were fed with a normal chow diet (NCD) or high-fat diet (HFD), and HFD-fed mice was supplemented with DMY once daily by intragastric gavage for 13 weeks. Serum lipopolysaccharide (LPS) was measured by ELISA, and expressions of tight junction proteins in colon and pro-inflammatory cytokines in liver and epididymal adipose tissues were determined by quantitative PCR. The gut microbiota was analyzed by 16S rDNA sequencing. Using the method combined gut microbiota depletion and repopulation in HFD-fed mice, the causation that DMY reduces obesity by targeting the gut microbiota was explored. Results: DMY reduced body weight gain, fat accumulation and hepatic steatosis, and improved glucose homeostasis and insulin sensitivity in HFD-fed mice. The metabolic endotoxemia, chronic low-grade inflammation and leaky gut were alleviated. DMY reverses the gut microbiota of HFD-fed mice to the composition similar with that of NCD-fed mice. Moreover, the beneficial effects of DMY on HFD-induced obesity were eliminated by gut microbiota depletion, and were subsequently restored together with the modulation of gut microbiota composition after microbiota repopulation. Conclusions: Supplementation of DMY from vine tea represents an effective and implementable strategy that modulates the potentially beneficial gut commensal bacteria to prevent obesity, non-alcoholic fatty liver disease and type 2 diabetes. Funding Statement: This study was financially supported by the National Natural Science Foundation of China (No. 81503013) and Natural Science Foundation of Hubei Province (No. 2017CFB481). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The animal experiment was approved by the Institutional Animal Care and Use Committee at Tongji Medical College, Huazhong University of Science and Technology (IACUC No. S769).