Yan Chao, Yao Yilong, Zhang Zhaobo, Li Fanqinyu, Fan Danyang, Liu Wen, Fan Xinhao, Xu Lingna, Liu Yanwen, Wang Shilong, Hu Mengling, Yang Yalan, Tang Zhonglin
Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Livestock and Poultry Multi-Omics of MARA, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, China.
Kunpeng Institute of Modern Agriculture at Foshan, Agricultural Genomics Institute, Chinese Academy of Agricultural Sciences, Foshan, China.
Gut Microbes. 2025 Dec;17(1):2545434. doi: 10.1080/19490976.2025.2545434. Epub 2025 Aug 18.
Skeletal muscle fiber composition is essential for maintaining muscle function and overall health. Growing evidence underscores the pivotal role of the gut-muscle axis in mediating the influence of gut microbiota on skeletal muscle development. However, the mechanisms underlying microbiota-mediated regulation of skeletal muscle fiber type remain unclear. Here, we employed multi-omics approaches, including RNA-seq, MeRIP-seq, 16S rRNA gene sequencing, and metabolomics, to investigate the causal relationship between the gut microbiota and skeletal muscle fiber transition. Our results demonstrate that the gut microbiota modulates skeletal muscle fiber transition by influencing N6-methyladenosine (mA) methylation to regulate the expression of the slow-twitch fiber marker . Specifically, METTL3-dependent mA methylation enhances gene expression, leading to an increased proportion of slow-twitch fibers and a reduction in fast-twitch fibers. Furthermore, the microbiota-derived methyl donor betaine promotes expression and () abundance, and facilitates fast-to-slow fiber conversion via mA modification. The transplantation of significantly altered betaine levels and mA modification, thereby promoting muscle fiber remodeling. In conclusion, these findings reveal that -coordinated betaine drives skeletal muscle fiber conversion by modulating mRNA expression. This study provides novel insights into the role of mA RNA methylation in the gut-muscle crosstalk, highlighting potential therapeutic targets for muscle-related disorders.
骨骼肌纤维组成对于维持肌肉功能和整体健康至关重要。越来越多的证据强调了肠-肌轴在介导肠道微生物群对骨骼肌发育影响方面的关键作用。然而，微生物群介导的骨骼肌纤维类型调节的潜在机制仍不清楚。在这里，我们采用了多组学方法，包括RNA测序、MeRIP测序、16S rRNA基因测序和代谢组学，来研究肠道微生物群与骨骼肌纤维转变之间的因果关系。我们的结果表明，肠道微生物群通过影响N6-甲基腺苷（m⁶A）甲基化来调节慢肌纤维标记物的表达，从而调节骨骼肌纤维转变。具体而言，依赖METTL3的m⁶A甲基化增强了基因表达，导致慢肌纤维比例增加，快肌纤维减少。此外，微生物群衍生的甲基供体甜菜碱促进了表达和（）丰度，并通过m⁶A修饰促进了快肌纤维向慢肌纤维的转变。的移植显著改变了甜菜碱水平和m⁶A修饰，从而促进了肌纤维重塑。总之，这些发现揭示了-协调的甜菜碱通过调节mRNA表达驱动骨骼肌纤维转变。这项研究为m⁶A RNA甲基化在肠-肌串扰中的作用提供了新的见解，突出了肌肉相关疾病的潜在治疗靶点。
