<i>Cordyceps militaris</i> Ethanol Extract Alleviates Hyperglycemia in Type 2 Diabetic Mice in Association With Gut Microbiota Modification

ABSTRACT Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder characterized by hyperglycemia and gut microbiota dysbiosis. This study evaluated the therapeutic effects of Cordyceps militaris ethanol extract (CME) on glycemic control and gut microbiota in a T2DM mouse model. After a 4‐week intervention, CME administration effectively ameliorated hyperglycemia, glucose intolerance, dyslipidemia and pancreatic islet dysfunction. Concurrently, CME treatment was associated with favorable alterations in the gut microbiota, notably a reduced Bacillota/Bacteroidota ratio and increased relative abundance of short‐chain fatty acid (SCFA)‐producing genera including Eubacterium‐ventriosum ‐group, Butyribacter and Candidatus‐Soleaferrea , which correlated with elevated SCFAs concentrations. In addition, CME treatment was associated with enhanced expression of akt‐1 and glut‐2 , which might be associated with increased SCFAs levels. These findings suggest that the observed upregulation of akt‐1 and glut‐2 expression may be linked to alterations in gut microbiota composition and increased SCFAs levels, which correlate with alleviated hyperglycemia. Correlation analysis further revealed that Lachnospiraceae‐NK4B4 ‐group, Candidatus Soleaferrea , Eubacterium‐ventriosum ‐group and Anaeroplasma were highly correlated with multiple hyperglycemia‐related biochemical indicators, suggesting their potential as microbial biomarkers for T2DM. Our findings provide correlational evidence supporting the potential of CME as a therapeutic agent.