Polysaccharides from Cordyceps militaris prevent obesity in association with modulating gut microbiota and metabolites in high-fat diet-fed mice

Improved gut microbes and nutritious metabolites have been considered as the mediators of health benefits from indigestible polysaccharides, but their role in the anti-obesity effect of polysaccharides from Cordyceps militaris (CMP) remains elusive. This study aims to explore the potential mediators of the anti-obesity effects of CMP in high-fat diet (HFD)-fed mice using 16S rRNA sequencing and untargeted metabolomics analysis. The results showed that CMP supplementation in HFD-fed mice reduced body weight, fat accumulation, pro-inflammatory cytokine levels, and impaired glucose tolerance as well as gut barrier. Moreover, the CMP reversed the HFD-induced gut microbiota dysbiosis, as indicated by the elevated population of Alloprevotella, Parabacteroides, Butyricimonas, and Alistipes; and decreased population of Negativebacillus, in addition to altered levels of metabolites, such as brassicasterol and 4′-O-methylkanzonol W. Notably, CMP prevented obesity in association with the altered gut microbes and metabolites. These findings suggest that CMP may serve as a potential prebiotic agent to modulate specific gut microbes and related metabolites, which play a critical role in its preventing obesity-related diseases.