Abstract
Dystrophin deficiency alters the sarcolemma structure, leading to muscle dystrophy, muscle disuse, and ultimately death. Beyond limb muscle deficits, patients with Duchenne muscular dystrophy have numerous transit disorders. Many studies have highlighted the strong relationship between gut microbiota and skeletal muscle. The aims of this study were: i) to characterize the gut microbiota composition over time up to 1 year in dystrophin-deficient mdx mice, and ii) to analyze the intestine structure and function and expression of genes linked to bacterial-derived metabolites in ileum, blood, and tibial anterior and soleus muscles to study interorgan interactions. Mdx mice displayed a significant reduction in the overall number of different operational taxonomic units and their abundance (α-diversity). Mdx genotype predicted 20% of β-diversity divergence, with a large taxonomic modification of the four phyla (Actinobacteria, Proteobacteria, Tenericutes, and Deferribacteres) and the included genera. Interestingly, intestinal motility and gene expressions of tight junction and Ffar2 receptor were down-regulated in the ileum of the mdx genotype. Concomitantly, inflammation related to gut microbiota was revealed by an up-regulation of circulating inflammatory markers (tumor necrosis factor, IL-6, and monocyte chemoattractant protein-1) and muscle inflammation Tlr4/Myd88 pathway (Toll-like receptor 4, which recognizes pathogen-associated molecular patterns, known as the bacterial metab- olites receptor). Finally, in mdx mice, adiponectin was reduced in blood and its receptor modulated in muscles. This study highlights a specific gut microbiota composition and highlights interorgan interactions in mdx physiopathology with gut microbiota as the potential central metabolic organ.