Ampelopsis grossedentata improves type 2 diabetes mellitus through modulating the gut microbiota and bile acid metabolism

Ampelopsis grossedentata is a flavonoid-rich healthy tea, traditionally used as a Chinese herbal medicine, that effectively treats T2DM. In the present study, we investigated the anti-diabetic effect of total flavonoids extracted from Ampelopsis grossedentata (AGT) and the underlying mechanisms using 16S rDNA sequencing and metabolomics. The results indicated that after AGT treatment for 6 weeks, the body weight, liver index, fasting blood glucose (FBG), OGTT-AUC, and serum lipid levels were reduced, and pathological injuries of the liver improved significantly in ZDF rats. Meanwhile, AGT increased the abundance and diversity of gut microbiota, especially BSH-active bacteria, which reduced T-beta-MCA and T-alpha-MCA levels and further activate FXR and FGF15. The activation of FXR-FGF15 axis inhibited excessive bile acid accumulation and liver gluconeogenesis upon AGT treatment. Taken together, our results suggested that AGT ameliorated glycolipid metabolism disorder via the "microbiota-gut-liver" axis, indicating that AGT may be a potential therapeutic strategy for treating T2DM.