Orally administered C. militaris ethanol extract (2.0 g kg-1) and cordycepin (50 mg kg-1) were associated with improved metabolic status and coordinated changes in gut microbial composition, serum metabolism, and bile acid-related molecular readouts in a T2DM-HLP mouse model over 6 weeks.
EAE and 50 mg kg-1 cordycepin reduced serum lipid and transaminase levels in T2DM-HLP mice compared to the model group.
EAE and 50 mg kg-1 cordycepin were associated with downward shifts in fasting blood glucose and oral glucose tolerance test curves in T2DM-HLP mice.
Histological alterations in the colon and liver were less apparent in EAE and 50 mg kg-1 cordycepin treatment groups compared to the model group.
Faecal 16S rDNA and ITS sequencing revealed changes in both bacterial and fungal community structure in treated mice.
Untargeted serum metabolomics identified distinct metabolic profiles in treated mice involving bile acids, fatty acids, amino acids, nucleotides, and redox-related metabolites.
EAE and cordycepin treatment was associated with increased colonic TGR5 and hepatic FXR immunoreactivity, along with altered expression of bile acid-related genes.
The relationship between cordycepin dose and metabolic response was not simply dose-dependent, with the 100 mg kg-1 dose showing less consistent responses than the 50 mg kg-1 dose.
The study used a T2DM accompanied by hyperlipidaemia (T2DM-HLP) mouse model to evaluate C. militaris ethanol extract and cordycepin over a 6-week oral administration period.
This research suggests that an ethanol extract from Cordyceps militaris (an edible medicinal mushroom) and one of its active compounds, cordycepin, may help improve metabolic problems associated with both type 2 diabetes and high blood lipids (hyperlipidaemia) in mice. Over a 6-week period, mice given the mushroom extract or a moderate dose of cordycepin (50 mg per kg body weight) showed lower blood sugar levels, better responses to a glucose challenge, reduced blood lipids, and less liver damage compared to untreated diabetic mice. Improvements were also seen in the physical appearance of colon and liver tissue under the microscope. The study found that these metabolic improvements were accompanied by coordinated changes in the gut microbiome — both bacterial and fungal communities shifted — as well as changes in blood metabolites related to bile acids, fats, and amino acids. At the molecular level, treatment appeared to activate bile acid signaling pathways (specifically proteins called TGR5 and FXR) and alter the expression of genes involved in cholesterol and bile acid metabolism in the liver. Interestingly, a higher dose of cordycepin (100 mg per kg) did not produce more consistent benefits than the lower dose, suggesting the relationship between dose and effect is not straightforward. This research suggests that Cordyceps militaris and its compound cordycepin may exert metabolic benefits partly by reshaping the gut microbial community and modulating how bile acids are produced and processed in the body. These findings are relevant because type 2 diabetes combined with high blood lipids is a common and difficult-to-manage condition, and natural food-based compounds that can address multiple aspects of this problem simultaneously are of growing interest. However, these findings are based on a mouse model, and further research would be needed to understand whether similar effects occur in humans.
Shi H, Meng Y, Zhang G, Ling J. (2026). Metabolic effects of Cordyceps militaris ethanol extract and cordycepin in mice with type 2 diabetes and hyperlipidaemia: gut microbial and bile acid-related changes.. Food & function. https://doi.org/10.1039/d6fo02540d