Mulberry leaf polysaccharides ameliorate glucose and lipid metabolism disorders via the gut microbiota-bile acids metabolic pathway.

Mulberry leaf polysaccharides (MLP) are integral components of Mulberry leaves that confer hypoglycemic and hypolipidemic properties. This study investigated the efficacy of MLP in treating Type 2 Diabetes Mellitus (T2DM) and the underlying mechanisms related to gut microbiota-bile acids metabolism in T2DM rats. The findings revealed that MLP apparently reduced fasting blood glucose and lipid levels, ameliorated disorders in glucose and lipid metabolism, and mitigated insulin resistance. MLP enhanced the abundance of Prevotella, Ruminococcus, and Lactobacillus, thereby rectifying the gut microbiota dysbiosis in rats, which effectively restored gut microbiota homeostasis and composition. Furthermore, the data demonstrated that MLP modulated bile acid metabolism, as evidenced by reduced serum cholesterol levels, enhanced mRNA expression of hepatic cholesterol 7α- hydroxylase (Cyp7a1) and cholesterol 12α- hydroxylase (Cyp8b1), and ileal G protein-coupled bile acid receptor (Tgr5), while suppressing hepatic and ileal farnesoid X receptor (Fxr) mRNA expression in T2DM rats. Additionally, MLP upregulated the protein expression of hepatic CYP7A1 and CYP8B1, and ileal TGR5, while inhibiting FXR protein levels in the liver and ileum of T2DM rats. These results suggest that MLP can rectify disorders in glucose and lipid metabolism via the gut microbiota-bile acids metabolic pathway.