Abstract
The gut microbiota represents a community of 1,014 bacteria that are essential for the host’ health. Its alteration, called dysbiosis, impacts various organs (intestine, liver, adipose tissue) leading to numerous diseases, in particular metabolic diseases. Skeletal muscle, a highly metabolic tissue responsible for our physical autonomy, also seems to be under its influence. This work is part of the emerging issue on the potential microbiota - skeletal muscle axis, and the understanding of its related mechanisms. Our results show that gut bacteria are essential for skeletal muscle function. In fact, depletion of the microbiota reduces ex-vivo muscle contractile capacities as well as muscle glycogen content, while natural reseeding normalizes all of these deleterious effects. 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 and to come closer to the pathophysiological reality. We therefore studied 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.Our metagenomic analyses reveal microbial signatures specific to each of the 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 thus strongly altered in the dystrophic mdx phenotype, with a more profound modification of the bacterial composition, with specific phylum presence : Deferribacteres; and modifications down to the genus for the Actinobacteria and Proteobacteria phyla. Interestingly, Muribaculaceae family is inversely affected in our opposite phenotypes : hypoetrophic (KO-mstn) and dystrophic (mdx). Moreover, in all three models, OTUs related to the Lachnospiraceae family are impacted suggesting an involvement in the muscle phenotype.After 5-days of Dry Immersion the Clostridiales, Lactobacillaceae and Selenomonadales orders of phylum Firmicutes 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. In conclusion, this thesis 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 the use of the gut microbiota as a vector for improving skeletal muscle function is thus possible opening up therapeutic perspectives for the numerous pathologies affecting the muscle tissue but also for the fields of sports performance.