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

Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin-deficient mice.
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菌群营养不良影响肌营养不良蛋白缺陷小鼠的免疫系统和肌肉病理生理学。

DOI:
10.15252/emmm.202216244
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发表时间:
2023-03-08
影响因子:
11.1
通讯作者:
Torrente, Yvan
Torrente, Yvan
中科院分区:
医学1区
文献类型:
--
作者:
Farini, Andrea;Tripodi, Luana;Villa, Chiara;Strati, Francesco;Facoetti, Amanda;Baselli, Guido;Troisi, Jacopo;Landolfi, Annamaria;Lonati, Caterina;Molinaro, Davide;Wintzinger, Michelle;Gatti, Stefano;Cassani, Barbara;Caprioli, Flavio;Facciotti, Federica;Quattrocelli, Mattia;Torrente, Yvan

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杜氏肌营养不良症(DMD)是一种进行性严重肌肉萎缩性疾病,由DMD突变引起,编码肌营养不良蛋白,导致肌肉功能丧失,伴心脏/呼吸衰竭和过早死亡。由于营养不良的肌肉是通过浸润的炎性细胞和肠道微生物群落可以引起免疫失调和代谢综合征,我们试图研究肠道细菌是否支持mdx营养不良小鼠模型中的肌肉免疫应答。我们强调了DMD疾病特征与普氏菌相对丰度之间的强相关性。此外,通过生成mdx无菌动物模型而缺乏肠道微生物,以及通过抗生素治疗调节微生物群落结构,影响了肌肉免疫和纤维化。具有益生菌群的mdx小鼠的肠道定殖足以减少炎症并改善肌肉病理学和功能。这项工作确定了肠道微生物群在DMD发病机制中的潜在作用。DMD患者对炎症事件的易感性不能仅仅由骨骼肌遗传缺陷来解释,而是有利于将慢性炎症的发展与表观遗传学因素和退行性环境之间的严格调节联系起来的新范式。
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. The susceptibility of DMD patients to inflammatory events cannot solely be explained by skeletal muscle genetic defects but rather favors a new paradigm linking the development of chronic inflammation with a strict regulation between epigenetics factors and degenerative environment.
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