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

Abstract

This study aims to explore the molecular mechanisms of <i>Lycium barbarum</i> 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 <i>Bacteroides</i>, <i>Ruminococcaceae_UCG-014</i>, <i>Intestinimonas</i>, <i>Mucispirillum</i>, <i>Ruminococcaceae_UCG-009</i> and decreasing the relative abundance of <i>Allobaculum</i>, <i>Dubosiella</i>, <i>Romboutsia</i>. 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, <i>Cetobacterium</i>, <i>Streptococcus</i>, <i>Ralstonia</i>. <i>Cetobacterium</i>, <i>Ruminiclostridium</i>, and <i>Bifidobacterium</i> correlated positively with insulin, whereas <i>Cetobacterium</i>, <i>Millionella</i>, <i>Clostridium_sensu_stricto_1</i>, <i>Streptococcus</i>, and <i>Ruminococcaceae_UCG_009</i> 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.