Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy

• DOI: 10.15252/emmm.202216225
• Publication Date: 2023-01-03T08:24:20Z
• Authors: Hilal Kalkan; Ester Pagano; Debora Paris; Elisabetta Panza; Mariarosaria Cuozzo; Claudia Moriello; Fabiana Piscitelli; Armita Abolghasemi; Elisabetta Gazzerro; Cristoforo Silvestri; Raffaele Capasso; Andrea Motta; Roberto Russo; Vincenzo Di Marzo; Fabio Arturo Iann...
• Keywords: 0301 basic medicine; autophagy; Medicine (General); short‐chain fatty acids; short-chain fatty acids; QH426-470; Mice; 03 medical and health sciences; R5-920; autophagy; duchenne muscular dystrophy; endocannabinoid system; gut microbiota; short-chain fatty acids; Genetics; Autophagy; Animals; endocannabinoid system; Muscle, Skeletal; duchenne muscular dystrophy; Inflammation; gut microbiota; Articles; 3. Good health; Muscular Dystrophy, Duchenne; Intestines; Mice, Inbred mdx; Integrative Biomedicine [Topic 3]; Dysbiosis; Function and Dysfunction of the Nervous System; Endocannabinoids

Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal composition along with circulating levels short-chain fatty acids (SCFAs) and related metabolites are altered mdx mouse model Duchenne muscular dystrophy (DMD) compared healthy controls. Supplementation sodium butyrate (NaB) mice rescued strength autophagy, prevented inflammation associated excessive endocannabinoid signaling at CB1 receptors to same extent as deflazacort (DFZ), standard palliative care for DMD. In LPS-stimulated C2C12 myoblasts, NaB reduces inflammation, promotes prevents dysregulation microRNAs targeting receptor gene, a manner depending on activation GPR109A PPARγ receptors. sum, propose novel disease-modifying approach DMD may have benefits also other dystrophies.