Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin-deficient mice

EMBO Mol Med. 2023 Mar 8;15(3):e16244. doi: 10.15252/emmm.202216244. Epub 2022 Dec 19.

Abstract

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 support the muscle immune response in mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. 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. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD.

Keywords: Duchenne muscular dystrophy; T-lymphocytes; gut microbiota; immunity; skeletal muscle metabolism.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dysbiosis
  • Dystrophin / genetics
  • Immune System / metabolism
  • Immune System / pathology
  • Mice
  • Mice, Inbred mdx
  • Microbiota*
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne* / genetics

Substances

  • Dystrophin

Associated data

  • GEO/GSE218370