This study investigated the therapeutic mechanism of oyster polysaccharide (OPS) on type 2 diabetes mellitus (T2DM). A T2DM mouse model was established through high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). The experimental mice were divided into six groups: normal control (NC), model control (MC), low-dose OPS (OPS-L), medium-dose OPS (OPS-M), high-dose OPS (OPS-H), and positive control (metformin, MET). Comprehensive evaluations were conducted, including blood glucose and lipid profiles, hepatic and renal histopathology, 16S rDNA-based gut microbiota analysis, and untargeted fecal metabolomics. Compared to the MC group, the OPS-L and OPS-M groups exhibited significant reductions in fasting blood glucose (FBG), fasting serum insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) (P<0.01, P<0.001), along with increased body weight (P<0.05). Serum levels of triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were reduced to varying degrees, with alleviated hepatic and renal tissue damage. Notably, the OPS-M group demonstrated the most pronounced hypoglycemic effects. OPS treatment modulated gut microbiota composition in T2DM mice, restoring α- and β-diversity indices toward NC group levels. Serum metabolomics revealed alleviated metabolic pathways involving histidine metabolism, alpha-linolenic acid metabolism, and ketone body synthesis/degradation. Correlation analysis identified significant associations between differential bile acid metabolites and specific bacterial taxa, particularly g_Muribaculaceae and g_Rikenellaceae_RC9_gut_group. This study indicates OPS ameliorates T2DM in mice through mechanisms potentially linked to gut microbiota modulation, fecal metabolite regulation, and alterations in serum bile acid profiles.
| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |