부산대학교 도서관

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 many transit disorders. Many studies 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 years-old, in dystrophin-deficient mdxmice; ii) to analyse the intestine structure-function and expression of genes linked to bacterial-derived metabolites in ileum, blood, tibial anterior and soleus muscles to study inter-organ interactions. Mdxmice showed a significant reduction in overall number of different Operational Taxa Units and their abundance (α-diversity). Mdxgenotype predicted 20% of β-diversity divergence, with a large taxonomic modification of the four phyla: Actinobacteria, Proteobacteria, Tenericutes, Deferribacteres and the included genera. Interestingly, intestinal motility and gene expressions of tight junction and Ffar2receptor were downregulated in ileum of mdxgenotype. Concomitantly, inflammation related to gut microbiota was revealed by an upregulation of circulating inflammatory markers (TNF, IL-6, MCP-1) and muscle-inflammation Tlr4/Myd88pathway (TLR4 known as bacterial metabolites receptor). Finally, in mdxmice, adiponectin was reduced in blood and its receptor modulated in muscles. This study highlights a specific gut microbiota composition and points out inter-organ interactions in mdxphysiopathology with gut microbiota as potential central metabolic organ.