Hypoglycemic Effects of Lycium barbarum Polysaccharide in Type 2 Diabetes Mellitus Mice via Modulating Gut Microbiota

This study aims to explore the molecular mechanisms of Lycium barbarum polysaccharide (LBP) in alleviating type 2 diabetes through intestinal flora modulation. A high-fat diet (HFD) combined with streptozotocin (STZ) was applied to create a diabetic model. The results indicated that LBP effectively alleviated the symptoms of hyperglycemia, hyperlipidemia, and insulin resistance in diabetic mice. A high dosage of LBP exerted better hypoglycemic effects than low and medium dosages. In diabetic mice, LBP significantly boosted the activities of CAT, SOD, and GSH-Px and reduced inflammation. The analysis of 16S rDNA disclosed that LBP notably improved the composition of intestinal flora, increasing the relative abundance of Bacteroides , Ruminococcaceae_UCG-014 , Intestinimonas , Mucispirillum , Ruminococcaceae_UCG-009 and decreasing the relative abundance of Allobaculum , Dubosiella , Romboutsia . LBP significantly improved the production of short-chain fatty acids (SCFAs) in diabetic mice, which corresponded to the increase in the beneficial genus. According to Spearman’s correlation analysis, Cetobacterium , Streptococcus , Ralstonia . Cetobacterium , Ruminiclostridium , and Bifidobacterium correlated positively with insulin, whereas Cetobacterium , Millionella , Clostridium_sensu_stricto_1 , Streptococcus , and Ruminococcaceae_UCG_009 correlated negatively with HOMA-IR, HDL-C, ALT, AST, TC, and lipopolysaccharide (LPS). These findings suggested that the mentioned genus may be beneficial to diabetic mice’s hypoglycemia and hypolipidemia. The up-regulation of peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and insulin were remarkably reversed by LBP in diabetic mice. The real-time PCR (RT-PCR) analysis illustrated that LBP distinctly regulated the glucose metabolism of diabetic mice by activating the IRS/PI3K/Akt signal pathway. These results indicated that LBP effectively alleviated the hyperglycemia and hyperlipidemia of diabetic mice by modulating intestinal flora.