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Here, we provide evidence that fecal microbiota composition along with circulating levels of short\u2010chain 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\u2010stimulated 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 PPAR\u03b3 receptors. In sum, we propose a novel disease\u2010modifying approach in DMD that may have benefits also in other muscular dystrophies.<\/jats:p>","DOI":"10.15252\/emmm.202216225","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T03:24:20Z","timestamp":1672716260000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy"],"prefix":"10.1038","volume":"15","author":[{"given":"Hilal","family":"Kalkan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"Pagano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4526-8353","authenticated-orcid":false,"given":"Debora","family":"Paris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0274-4671","authenticated-orcid":false,"given":"Elisabetta","family":"Panza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariarosaria","family":"Cuozzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9975-4918","authenticated-orcid":false,"given":"Claudia","family":"Moriello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9343-4622","authenticated-orcid":false,"given":"Fabiana","family":"Piscitelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armita","family":"Abolghasemi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Gazzerro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristoforo","family":"Silvestri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3335-1822","authenticated-orcid":false,"given":"Raffaele","family":"Capasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8643-658X","authenticated-orcid":false,"given":"Andrea","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5950-1617","authenticated-orcid":false,"given":"Roberto","family":"Russo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1490-3070","authenticated-orcid":false,"given":"Vincenzo","family":"Di Marzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4480-8370","authenticated-orcid":false,"given":"Fabio Arturo","family":"Iannotti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,3]]},"reference":[{"key":"BFEMMM202216225_CR1","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1186\/1757-4749-6-25","volume":"6","author":"S Alkadhi","year":"2014","unstructured":"Alkadhi S, Kunde D, Cheluvappa R, Randall\u2010Demllo S, Eri R (2014) The murine appendiceal microbiome is altered in spontaneous colitis and its pathological progression. 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