Abstract: BACKGROUND: Lycium barbarum polysaccharide is a natural active ingredient with potential to lower blood glucose and improve diabetes-related symptoms. However, from the perspective of gut microbiota, the underlying factors for the effects of Lycium barbarum polysaccharide on glycolipid abnormalities have not been fully elucidated.
OBJECTIVE: To investigate the effect of Lycium barbarum polysaccharide on type 2 diabetes mellitus and its related mechanism.
METHODS: Six male Sprague-Dawley rats aged 8 weeks were randomly selected from 18 rats to form a blank control group. The remaining 12 rats were fed a high-sugar, high-fat diet for 8 weeks and then received a single tail vein injection of 1% streptozotocin to establish a type 2 diabetes model. After successful modeling, the rat models were then randomly divided into a model control group (n=6) and a Lycium barbarum polysaccharide group (n=6). Rats in the Lycium barbarum polysaccharide group were administered Lycium barbarum polysaccharide solution via gavage at a dose of 200 mg/(kg·d), 2 mL per dose, once daily, for 12 consecutive weeks. After the intervention, rat serum and feces were collected. 16S rDNA sequencing was used to analyze the gut microbiota, and α diversity, β diversity and principal component analysis were used to characterize the abundance and structural characteristics of the microbiota. Liquid chromatography-mass spectrometry was used to detect the level of short-chain fatty acids. The indicators of glucose and lipid metabolism, insulin resistance and inflammatory response were detected by ELISA.
RESULTS AND CONCLUSION: (1) Compared with the model control group, Lycium barbarum polysaccharide could increase the level of high-density lipoprotein cholesterol, reduce the levels of total cholesterol, triglyceride and low-density lipoprotein cholesterol, indicating Lycium barbarum polysaccharide improves lipid accumulation and inhibits body mass loss in type 2 diabetic rats. (2) Compared with the model control group, Lycium barbarum polysaccharide reduced the levels of interleukin-6, tumor necrosis factor-α and blood glucose, and increased the levels of insulin and glucagon-like peptide-1, indicating that Lycium barbarum polysaccharide effectively inhibits inflammation and insulin resistance. (3) Lycium barbarum polysaccharide significantly improved the composition of gut microbiota, increased the abundance of Lachnospiraceae_NK4A136_group, Clostridia_UCG-014_unclassified, Monoglobus, Phascolarctobacterium, Candidatus_Saccharimon, Desulfovibrionaceae unclassified, and Desulfovibrio, decreased the abundance of Muribaculaceae_unclassified and Enterorhabdus. (4) Lycium barbarum polysaccharide also significantly increased the level of short-chain fatty acids. Clostridia_UCG-014_unclassified, Candidatus_Saccharimonas and Muribaculaceae_unclassified may be involved in regulating the production of butyrate, thereby improving glucose and lipid metabolism in type 2 diabetic rats, whereas Lachnospiraceae_NK4A136_group, Monoglobus and Desulfovibrionaceae unclassified may be involved in regulating the production of isobutyl acid to inhibit insulin resistance and improve lipid metabolism. (5) Lycium barbarum polysaccharide can improve inflammation in type 2 diabetic rats by increasing the abundance of Firmicutes_unclassified, Clostridia_UCG-014_unclassified, Intestinimona and Colidextribacter, and inhibiting the abundance of Kineothrix.

Key words: Lycium barbarum polysaccharide, gut microbiota, type 2 diabetes mellitus, short-chain fatty acids, glucose and lipid metabolism, inflammation