Abstract
Gut microbiota is involved in the development of several chronic diseases, including diabetes, obesity and cancer, through its interactions with the host organs. It has been suggested that the cross-talk between gut microbiota and skeletal muscle plays a role in different pathological conditions, such as intestinal chronic inflammation and cachexia. However, it remains unclear whether gut microbiota directly influences skeletal muscle function. In this work, we studied the impact of gut microbiota modulation on mice skeletal muscle function and investigated the underlying mechanisms. We determined the consequences of gut microbiota depletion after treatment with a mixture of broad spectrum antibiotics for 21 days and after 10-days natural reseeding. We found that in gut microbiota-depleted mice, running endurance was decreased, as well as the extensor digitorum longus muscle fatigue index in an ex vivocontractile test. Importantly, the muscle endurance capacity was efficiently normalized by natural reseeding. Theseendurance changes werenot relatedto variationin muscle mass, fiber typology or mitochondrial function. However, several pertinent glucose metabolism markers such as ileum gene expression of short fatty acidchain and glucose transporters,Gpr41and Sglt1and muscle glycogen level, paralleled the muscle endurance changes observed after ATB treatment and reseeding. As glycogen is a key energetic substrate for prolonged exercise, modulating itsmuscle availability via gut microbiota represents one potent mechanism that can contribute to the gut microbiota/skeletal muscle axis. Taken together, our results strongly support the hypothesis that gut bacteria are required for host optimal skeletal muscle function.