This study is based on intestinal flora-host metabolism and deeply explores the mechanism of Shanzhuyu (Corni Fructus) polysaccharides in type 2 diabetes.

A type 2 diabetes model was established by high sugar and high fat feed combined with a small dose of intraperitoneal injection of streptozocin (STZ). The pharmacoefficiency index of the rats in each group was detected, and the intestinal microbial structure of the rats in each group was detected by 16S rDNA sequencing technology, and the content of short-chain fatty acids (SCFAs) was measured in combination with GC-MS technology. The Western Blot method was used to detect the protein levels of G-protein coupled receptor 43 (GPR43), G-protein coupled receptor 41 (GPR41) and glucagon-like peptide-1 (GLP-1) in liver tissues. Small molecule metabolomics study was performed on animal feces in each group using UPLC-MS/MS technology, and the correlation analysis was conducted on intestinal microbiota and differential metabolites.

The results of the drug efficacy index test showed that Shanzhuyu (Corni Fructus) polysaccharides could significantly reduce the blood sugar, blood lipids and inflammatory factors in the rats with type 2 diabetes. The results of intestinal flora sequencing showed that Shanzhuyu (Corni Fructus) polysaccharides significantly improved the bacterial diversity of type 2 diabetes rats. At the level of phylum, the abundance of Firmicutes, Bacteroides, Varves and Actinomycetes all had different degrees of correction, and the ratio of Firmicutes/Bacteroides increased significantly (P<0.05). At the level of genus, Lactobacillus, Akermans, Bacteroides and Muribaculaceae increased. The results of SCFAs and key metabolic pathways showed that the content of SCFAs in the feces of type 2 diabetes rats had significantly decreased (P<0.01), the protein expressions of GPR43, GPR41 and GLP-1 were significantly reduced (P<0.01), and after the intervention of Shanzhuyu (Corni Fructus) polysaccharides, the SCFAs content was significantly increased (P<0.05, P<0.01), and the protein expressions of GPR41, GPR43 and GLP-1 were significantly increased (P<0.01). Metabolomics screened differential metabolites with significant changes (P<0.05) among 46 model and control groups, mainly enriched 19 metabolic pathways such as sphingolipid metabolism and steroid biosynthesis. The results of the joint analysis showed that intestinal flora had a significant regulatory effect on differential metabolites such as sphingolipid metabolism and steroid biosynthesis, involving metabolic pathways such as sphingolipid metabolism and steroid biosynthesis.

Shanzhuyu (Corni Fructus) polysaccharides can affect the levels of metabolites such as SCFAs and sphingosine by regulating the intestinal microbiota structure, and then regulate the metabolism pathways such as short-chain fatty acid metabolism, sphingolipid metabolism and steroid biosynthesis, improve the protein expressions of GPR43, GPR41 and GLP-1, regulate the blood sugar and blood lipid levels of the rats, thereby regulating glycolipid metabolism and intestinal disorders, inhibiting the body's inflammatory response, reducing insulin resistance and playing a role in treating type 2 diabetes.