Duchenne muscular dystrophy (DMD) is a progressive severe muscle-wasting disease caused by mutations in DMD gene, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. In DMD patients, the lack of dystrophin determines a severe impairment of the intestinal homeostasis that could lead to a modulation of the inflammatory environment. Since immune system dysregulation was recently shown as a fundamental component of DMD pathogenesis we investigated the gut microbiota composition of dystrophic mice and its effects on muscle metabolism and function. We highlighted that gut microbiota–specific alterations (dysbiosis) correlate with the dystrophic pathology in mdx mice, also influencing muscle metabolism.
Furthermore, the absence of gut microbes through the generation of mdx germ-free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Dysbiotic microbiota of mdx negatively affected intestinal, spleen, and muscle inflammation following injection in wild-type mice; conversely, intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function.
In line with these results, the study of pathological alterations in the immune system-microbiota axis in mdx mice highlights the importance of microbiota as a potential target for therapeutic interventions.
With our approach, we had the opportunity to decipher the fundamental molecular pathways underlying immune system-microbiota and provided the scientific community with valuable insights how intestinal microbiota shape the inflammatory response and confers distinct susceptibility to muscle pathology. We trust in this work to identify novel biomarkers linked to gastrointestinal involvement and predictors of disease progression; next, we hope to translate our evidences into humans, to enable patients’ stratification according to the type of treatments they should benefit the most.
Our results will also inform the design of innovative therapeutic strategies, useful in delivering improved care for DMD and in sustaining a more rational and socioeconomic management of this disease.
You can read the complete article here: Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice | EMBO Molecular Medicine (embopress.org)