In-depth investigation of the hypoglycemic mechanism of Morchella importuna polysaccharide via metabonomics combined with 16S rRNA sequencing

Increasing evidence indicates that type 2 diabetes mellitus (T2DM) is closely related to intestinal bacteria disorders and abnormal hepatic metabolism. Morchella importuna polysaccharide (MIP) shows excellent hypoglycemic activity in vitro. However, the hypoglycemic effect and mechanism of MIP in vivo have yet to be investigated. In this study, the blood glucose, blood lipid and insulin resistance of diabetic mice after MIP intervention were measured to evaluate its hypoglycemic effect. Then, the microbiome and metabolomics were combined to explore the hypoglycemic mechanism of MIP. Results indicated that high dose MIP (400 mg/kg) had significant hypoglycemic effect. Furthermore, MIP could reverse diabetes-induced intestinal disorder by increasing the abundance of Akkermansia, Blautia, Dubosiella, and Lachnospiraceae, as well as decreasing the abundance of Helicobacteraceae. Besides, the hepatic metabolites and complex network systems formed by multiple metabolic pathways were regulated after MIP treatment. Notably, a new biomarker of diabetes (N-P-coumaroyl spermidine) was discovered in this study. Moreover, the significant association between intestinal bacteria and hepatic metabolites was determined by correlations analysis, which in turn confirmed MIP alleviated T2DM via the gut-liver axis. Therefore, these findings elucidated in-depth hypoglycemic mechanisms of MIP and provided a new biomarker for the prevention of diabetes.