Deciphering the potential role of Maca compounds prescription influencing gut microbiota in the management of exercise-induced fatigue by integrative genomic analysis

Abstract

A growing number of nutraceuticals and cosmeceuticals have been utilized for millennia as anti-fatigue supplements in folk medicine. However, the anti-fatigue mechanism underlying is still far from being clearly explained. The aim of the study is to explore the underlying mechanism of the Maca compound preparation (MCP), a prescription for management of exercise-induced fatigue. In this study, mice weight-loaded swimming test was used to evaluate the anti-fatigue effect of MCP. MCP significantly improved the forelimb grip strength and Rota-rod test in behavioral tests <i>via</i> regulating energy metabolism. 16S rDNA sequencing results showed MCP can regulate the intestinal flora at the genus level by increasing several beneficial bacteria (i.e., <i>Lactobacillus</i>, <i>Akkermansia</i> and etc.), and decreasing the harmful bacteria (i.e., <i>Candidatus_Planktophila</i> and <i>Candidatus_Arthromitus</i>), where notable high relevance was observed between the fatigue-related biomarkers and fecal microbiota. The results of microbial function analysis suggested that MCP might improve exercise-induced fatigue by enhancing energy metabolism, carbohydrate and lipid metabolism and metabolism of terpenoids and polyketides and breakdown of amino acid metabolism. In addition, and H₂O₂-induced oxidative stress model on C2C12 cells was employed to further validate the regulation of MCP on energy metabolisms. MCP pre-treatment significantly reduced intracellular ROS accumulation, and increased glycogen content, ATP generation capacity and mitochondrial membrane potential of skeletal muscle cells, as well as conferred anti-cell necrosis ability. In conclusion, MCP plays a key role in regulating fatigue occurrence in exercising and gut microbiota balance, which may be of particular importance in the case of manual workers or sub-healthy populations.