Helmholtz Gemeinschaft


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

PDF (Original Article) - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader
[img] Other (Supporting Information)

Item Type:Article
Title:Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy
Creators Name:Kalkan, H. and Pagano, E. and Paris, D. and Panza, E. and Cuozzo, M. and Moriello, C. and Piscitelli, F. and Abolghasemi, A. and Gazzerro, E. and Silvestri, C. and Capasso, R. and Motta, A. and Russo, R. and Di Marzo, V. and Iannotti, F.A.
Abstract:Nothing is known about the potential implication of gut microbiota in skeletal muscle disorders. Here, we provide evidence that fecal microbiota composition along with circulating levels of short-chain fatty acids (SCFAs) and related metabolites are altered in the mdx mouse model of Duchenne muscular dystrophy (DMD) compared with healthy controls. Supplementation with sodium butyrate (NaB) in mdx mice rescued muscle strength and autophagy, and prevented inflammation associated with excessive endocannabinoid signaling at CB1 receptors to the same extent as deflazacort (DFZ), the standard palliative care for DMD. In LPS-stimulated C2C12 myoblasts, NaB reduces inflammation, promotes autophagy, and prevents dysregulation of microRNAs targeting the endocannabinoid CB1 receptor gene, in a manner depending on the activation of GPR109A and PPARγ receptors. In sum, we propose a novel disease-modifying approach in DMD that may have benefits also in other muscular dystrophies.
Keywords:Autophagy, Duchenne Muscular Dystrophy, Endocannabinoid System, Gut Microbiota, Short-Chain Fatty Acids, Animals, Mice
Source:EMBO Molecular Medicine
Publisher:EMBO Press / Wiley
Page Range:e16225
Date:8 March 2023
Official Publication:https://doi.org/10.15252/emmm.202216225
PubMed:View item in PubMed

Repository Staff Only: item control page


Downloads per month over past year

Open Access
MDC Library