Bacteroides acidifaciens derived succinate mediates Gypenoside polysaccharides induced muscle fiber switching and exercise endurance enhancement

Enhancing exercise endurance holds significant practical importance for improving the physical fitness of the general population to cope with daily challenges, as well as boosting the physical capacity and quality of life of patients with relevant diseases. The regulation of Gynostemma pentaphyllum polysaccharides (GPMP) and gut microbiota can increase the expression of slow-twitch muscle fibers, yet the underlying mechanism remains to be explored. Herein, we demonstrate that GPMP enriches Bacteroides acidifaciens (B. acidifaciens) in the mouse gut, and this enrichment exhibits a significant correlation with muscle endurance. Subsequently, we identified that succinate, a key metabolite of B. acidifaciens, effectively enhances exercise endurance and the antioxidant capacity of muscles in mice, protecting them from damage caused by strenuous exercise. This key metabolite enters the circulatory system, acts on skeletal muscle, activates the non-canonical Wnt signaling pathway, increases the number of slow-twitch muscle fibers, and elevates the level of oxidative phosphorylation in muscle tissue, thereby enhancing exercise endurance. Furthermore, we also observed a similar increase in B. acidifaciens and succinate levels in the feces and serum of endurance athletes. In conclusion, these findings reveal that GPMP regulates the body's exercise endurance through specific gut microbes and their metabolites, establishing a regulatory mechanism of gut microbiota on the host's exercise endurance.