Flavonoids-Rich Extracts from Chuju (<em>Asteraceae Chrysanthemum </em>L.) Alleviate Disturbance of Glycolipid Metabolism on Type 2 Diabetic Mice via Modulating the Gut Microbiota

The prevention of type 2 diabetes mellitus (T2DM) and its associated complications is an urgent public health issue that affects hundreds of millions of people globally. Chuju has been proved to possess antihyperglycemic activity. However, the bioactive ingredients in chuju that contribute to antihyperglycemic activity as well as the relation between its antihyperglycemic activity and gut microbiota remain unclear. To understand the potential effect it has on T2DM, the glycolipid metabolism and gut microbiota regulation of flavonoids-rich extracts from chuju (CJE) were investigated. The results showed that CJE remarkably mitigated hyperglycemia and glycolipid metabolism by regulating the gut microbiota in T2DM mice. Furthermore, the macro-genome sequencing results showed that CJE intervention regulated the composition of gut microbiota in T2DM mice, characterized by downregulating the abundance of Faecalibaculum, Coriobacteriaceae, Romboutsia and up-regulating the abundance of Alistipes. In addition, CJE could promote glycogen synthesis, gluconeogenesis, glucose transport and inhibite glycolysis by regulating the expression of insulin-mediated IRS1-PI3K-Akt-FoxO1/GSK 3β pathway and non-insulin-mediated AMPK-GLUT4 pathway. Taken together, the results provided new evidence that CJE alleviate disturbance of glycolipid metabolism via regulating gut microbiota and mediating IRS1-PI3K-Akt-FoxO1/GSK 3β, AMPK-GLUT4 pathway.