Hypoglycemic and hypolipidemic activities of Grifola frondosa polysaccharides and their relationships with the modulation of intestinal microflora in diabetic mice induced by high-fat diet and streptozotocin

Abstract This study aimed to investigate the hypoglycemic and hypolipidemic activities of polysaccharides from Grifola frondosa (GFP) in diabetic mice induced by high-fat diet (HFD) and streptozotocin (STZ). Results showed that oral administration of GFP markedly reduced the serum levels of fasting blood glucose (FBG), oral glucose tolerance (OGT), cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), and significantly decreased the hepatic levels of TC, TG and free fatty acids (FFA). Meanwhile, high-dose of GFP supplementation (900 mg/kg day) also showed powerful effects on moderating the composition of intestinal microflora in diabetic mice, especially altering the functionally relevant intestinal microbial phylotypes. Spearman's correlation network analysis revealed that key microbial phylotypes responding to GFP intervention were strongly correlated with the glucose and lipid metabolic disorders associated parameters. Moreover, GFP treatment regulated mRNA expression levels of the genes responsible for hepatic glucose and lipid metabolism. It is noteworthy that GFP treatment markedly increased mRNA expression of cholesterol 7α-hydroxylase (CYP7A1) and bile salt export pump (BSEP), suggesting an enhancement of bile acids (BAs) synthesis and excretion in liver. These findings demonstrated that GFP could prevent hyperglycemia and hyperlipidemia in diabetic mice by altering gut microbiota and regulating hepatic glycolipid metabolism related genes, and therefore could be used as potential functional food ingredients for the prevention or treatment of hyperglycemia and hyperlipidemia.