Abstract
Supplementation of polysaccharides is a promising gut microbiota-targeted therapeutic method for obesity and metabolic diseases. Biological activities of Cordyceps militaris polysaccharides have been well reported, but the effect of selenium (Se)-rich C. militaris polysaccharides (SeCMP) on obesity and associated metabolic disorder and gut microbiota composition has been rarely studied. This study aimed to investigate the anti-obesity and gut microbiota modulatory effect of crude polysaccharides separated from Se-rich C. militaris on a high-fat diet (HFD)-fed C57BL/6J mice model. Mice were treated with a normal diet (CHOW), HFD alone, HFD plus C. militaris polysaccharides (CMP), or low/medium/high dosage of SeCMP for 8 weeks. Body weight, fat content, serum lipid, appetite hormone, lipid gene expression, inflammation cytokines, thermogenic protein, short-chain fatty acids (SCFAs), and gut microbiota structure of the mice were determined. Compared with HFD-fed mice, the serum triglyceride and low-density lipoprotein cholesterol (LDL-C) in the SeCMP-200 group were decreased by 51.5% and 44.1%, respectively. Furthermore, serum lipopolysaccharide-binding proteins (LBP), adiponectin level, and pro-inflammation gene expression in the colon and subcutaneous fat were inhibited, whereas anti-inflammation gene expression was improved, reflecting SeCMP-200 might mitigate obese-induced inflammation. Meanwhile, SeCMP-200 promoted satiety and thermogenesis of obese mice. It also significantly decreased gut bacteria, such as Dorea, Lactobacillus, Clostridium, Ruminococcus, that negatively correlated with obesity traits and increased mucosal beneficial bacteria Akkermansia. There was no significant difference between CMP and SeCMP-100 groups. Our results revealed a high dose of SeCMP could prevent HFD-induced dyslipidemia and gut microbiota dysbiosis and was potential to be used as functional foods.