Cordyceps militaris polysaccharides alleviate hyperglycemia in type 2 diabetes mellitus mice by modulating gut...

Type 2 diabetes mellitus (T2DM) involves pancreatic dysfunction and hyperglycemia, leading to hepatic impairment and gut dysbiosis. Cordyceps militaris (C. militaris) possesses polysaccharides (CMP) with hypoglycemic and hypolipidemic effects. However, the potential of C. militaris to reconfigure gut microecology in T2DM remains inadequately explored. This study assessed the therapeutic effects of CMP on glucose homeostasis and microbial composition using a high-sugar and high-fat diet combined with streptozotocin-induced T2DM in a mouse model. Structural characterization identified CMP as a heteropolysaccharide with a molecular weight of 26,336 Da, predominantly composed of mannose (49.27%) and galactose (42.13%) connected by →6)-α-Manp-(1→ glycosidic bonds. Results indicated that a four-week CMP intervention significantly alleviated hyperglycemic symptoms, evidenced by marked reductions in fasting blood glucose (FBG), the area under the curve (AUC) of the oral glucose tolerance test (OGTT), and glycated serum protein (GSP). CMP administration notably enhanced insulin sensitivity and pancreatic function, as reflected in HOMA-IS, HOMA-IR, and HOMA-β indices. Additionally, lipid profiles in both serum and liver were normalized. The high-dose group (CMP-H) exhibited greater efficacy than the low-dose group (CMP-L). High-throughput sequencing analysis revealed that CMP effectively rebalanced gut microbiota by modulating the Bacillota/Bacteroidetes ratio and suppressing the proliferation of harmful taxa, specifically Adlercreutzia and Intestinimonas. Correlation analysis highlighted two microbial markers, Anaerotruncus and Enterocloster, which demonstrated robust negative correlations with lipid parameters (serum TC and liver LDL-c) and strong positive associations with pancreatic function indices. Collectively, these findings suggest that CMP alleviates T2DM symptoms by modulating the gut microbiota and restoring metabolic homeostasis.