Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice
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 cell...
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| Format: | Article |
| Language: | English |
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Springer Nature
2022-12-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202216244 |
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| author | Andrea Farini Luana Tripodi Chiara Villa Francesco Strati Amanda Facoetti Guido Baselli Jacopo Troisi Annamaria Landolfi Caterina Lonati Davide Molinaro Michelle Wintzinger Stefano Gatti Barbara Cassani Flavio Caprioli Federica Facciotti Mattia Quattrocelli Yvan Torrente |
| author_facet | Andrea Farini Luana Tripodi Chiara Villa Francesco Strati Amanda Facoetti Guido Baselli Jacopo Troisi Annamaria Landolfi Caterina Lonati Davide Molinaro Michelle Wintzinger Stefano Gatti Barbara Cassani Flavio Caprioli Federica Facciotti Mattia Quattrocelli Yvan Torrente |
| author_sort | Andrea Farini |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-8357d2ca59ce4c1ba595e9a4a19bc72c |
| institution | Kabale University |
| issn | 1757-4676 1757-4684 |
| language | English |
| publishDate | 2022-12-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj-art-8357d2ca59ce4c1ba595e9a4a19bc72c2024-11-10T12:37:36ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842022-12-0115312410.15252/emmm.202216244Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient miceAndrea Farini0Luana Tripodi1Chiara Villa2Francesco Strati3Amanda Facoetti4Guido Baselli5Jacopo Troisi6Annamaria Landolfi7Caterina Lonati8Davide Molinaro9Michelle Wintzinger10Stefano Gatti11Barbara Cassani12Flavio Caprioli13Federica Facciotti14Mattia Quattrocelli15Yvan Torrente16Neurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoStem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of MilanStem Cell Laboratory, Department of Pathophysiology and Transplantation, Dino Ferrari Center, University of MilanMucosal Immunology Lab, Department of Experimental Oncology, IEO‐European Institute of OncologyHumanitas UniversityTranslational Medicine – Department of Transfusion Medicine and Hematology, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoDepartment of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of SalernoDepartment of Medicine, Surgery and Dentistry, Scuola Medica Salernitana, University of SalernoCenter for Surgical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoNeurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoMolecular Cardiovascular Biology Division, Heart Institute, Cincinnati Children's Hospital Medical CenterCenter for Surgical Research, Fondazione IRCCS Ca' Granda, Ospedale Maggiore PoliclinicoHumanitas Clinical and Research Center IRCCSUnit of Gastroenterology and Endoscopy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Policlinico di MilanoUnit of Gastroenterology and Endoscopy, Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca' Granda, Ospedale Policlinico di MilanoMolecular Cardiovascular Biology Division, Heart Institute, Cincinnati Children's Hospital Medical CenterNeurology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore PoliclinicoAbstract 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.https://doi.org/10.15252/emmm.202216244Duchenne muscular dystrophygut microbiotaimmunityskeletal muscle metabolismT‐lymphocytes |
| spellingShingle | Andrea Farini Luana Tripodi Chiara Villa Francesco Strati Amanda Facoetti Guido Baselli Jacopo Troisi Annamaria Landolfi Caterina Lonati Davide Molinaro Michelle Wintzinger Stefano Gatti Barbara Cassani Flavio Caprioli Federica Facciotti Mattia Quattrocelli Yvan Torrente Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice EMBO Molecular Medicine Duchenne muscular dystrophy gut microbiota immunity skeletal muscle metabolism T‐lymphocytes |
| title | Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice |
| title_full | Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice |
| title_fullStr | Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice |
| title_full_unstemmed | Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice |
| title_short | Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice |
| title_sort | microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin deficient mice |
| topic | Duchenne muscular dystrophy gut microbiota immunity skeletal muscle metabolism T‐lymphocytes |
| url | https://doi.org/10.15252/emmm.202216244 |
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