effects of microbiome dysbiosis on murine dystrophic muscle

Duchenne muscular dystrophy (DMD) is a progressive severe muscle-wasting disease caused by mutations in DMD encoding dystrophin that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria may support the muscle immune response in mdx dystrophic animal model. We assess this question here through unbiased profiling of muscle transcriptome through RNAseq. We found that the absence of gut microbes through the generation of a mdx GF animal model as well as modulation of the microbial community structure by antibiotic treatment revealed the ability of the dystrophic-associated intestinal microbiota to modulate immunity and secondary muscle pathogenetic mechanisms of DMD, including inflammation, fibrosis, and atrophy. Overall design: 3 male mdx mice (3mo); 3 male mdx mice germ-free (3mo); 3 male mdx mice with antibiotics (3mo); 3 male WT mice (3mo); 3 male mdx mice (9mo); 2 male mdx mice germ-free (9mo); 3 male mdx mice with antibiotics (9mo).