Résumé
Introduction: The gut microbiota represents a community of 1014 bacteria that are essential for the host’ health [Cani, 2010]. Its alteration, called dysbiosis, impacts various organs (intestine, liver, adipose tissue) leading to numerous diseases, in particular metabolic diseases [Marchesi et al., 2016]. Skeletal muscle, a highly metabolic tissue responsible for our physical autonomy, also seems to be under its influence [Bindels & Delzenne, 2012]. Our laboratory works on the emerging issue on the potential gut microbiota - skeletal muscle axis, and the understanding of its related mechanisms. We previously showed that gut bacteria are essential for skeletal muscle function. In fact, depletion of the microbiota reduces ex-vivo muscle endurance as well as muscle glycogen content, while natural reseeding normalizes all of these deleterious effects [Nay & Jollet et al., 2019]. Understanding the functional relationship between these two organs also requires to analyze it in remarkable muscle phenotypes in order to reveal the nature and the extent of the relation. Methods: we studied thus the composition of the gut microbiota, the function and structure of the gut and the mechanistic links with skeletal muscle in myostatin-deficient hypertrophic mice (KO-mstn), dystrophic mdx mice, and in humans with an original model of accelerated hypoactivity “Dry Immersion”, in collaboration with the Centre National d'Etudes Spatiales [Jollet et al., 2021]. Results: Our metagenomic analyses reveal specific microbial signatures to each muscle phenotypes studied. It suggested that the chronicity of muscle damage is a factor in the importance of the composition changes observed in the gut microbiota. Diversity markers are strongly altered in the dystrophic mdx phenotype, with a more profound modification of the bacterial composition, with specific phylum presence: Deferribacteresp; and modifications down to the genus for the Actinobacteriap and Proteobacteriap phyla. Interestingly, Muribaculaceaef family is inversely affected in our opposite phenotypes: hypertrophic (KO-mstn) and dystrophic (mdx). Moreover, in all three models, OTUs (Operational Taxa Units) related to the Lachnospiraceaef family are impacted suggesting an involvement in the muscle phenotype. After Dry Immersion, the Clostridialeso, Lactobacillaceaeo orders of phylum Firmicutesf are modified. These differential gut microbiotas are sometimes associated with changes in the function and structure of the intestine, the only real barrier with skeletal muscle, as well as with a reduce production of short-chain fatty acids and overexpression of Fiaf and inflammatory markers, potentially related to muscle phenotypes. Conclusion: in overall, these results shed new light on the gut microbiota – skeletal muscle axis, which can be redefined as a reciprocal cross-talk, with clues to the underlying mechanisms. To envisage gut microbiota as a vector for improving skeletal muscle function is possible, opening up thus therapeutic perspectives for numerous pathologies affecting muscle tissue as well as sport performances.