Dystrophic Skeletal Muscle Phenotypes Can Be Horizontally Transferred via Fecal Microbiome Transplantations.

Abstract

Duchenne muscular dystrophy (DMD) has no cure and accounts for > 80% of muscular dystrophy cases around the world. DMD patients experience severe muscle degeneration that continues until death and also suffer from gastrointestinal complications that undoubtedly impact their microbiotas. It is unclear whether dystrophic microbiotas simply reflect the disease or whether microbes are directly involved in muscle phenotypes. Here, we sought to determine the microbiota's causal role in promoting dystrophic muscles by performing intra/inter-genotype fecal microbiota transplantations (FMT) between wildtype and mdx mice; assessing FMT's impact on muscles and microbiotas over 9 weeks. Transplanting mdx microbiotas into wildtype mice induced an mdx-like muscle phenotype while the inverse improved muscle features. We identified several taxa differentially abundant between wildtype mice receiving either wildtype or mdx FMT, highlighting their potential role in muscle health. Our results highlight the active role microbes have in impacting muscle health through both beneficial and detrimental mechanisms. Accordingly, microbes represent unexploited therapeutic targets for improving health outcomes in muscular dystrophies.