Microbiota-associated metabolite pantothenic acid enhances skeletal muscle contusion repair via epigenetic regulation of macrophage M2 polarization

作者：Lei Wu, Yu Shrike Zhang, Guowei Zhang, Xiaowei Feng, Weihao Zhu, Hua Yang, Xin Ji, Meifang Yin, Shujin Li, Yingmin Li, Weibo Shi, Bin Cong · 发表于：Journal of Translational Medicine · 年份：2026 · DOI：10.1186/s12967-026-08087-0 · 被引用次数：1 · 研究领域：Muscle Physiology and Disorders、Immune cells in cancer、Gut microbiota and health

BACKGROUND: The quality of skeletal muscle contusion repair hinges on the timely resolution of inflammation and the initiation of regeneration, processes in which M2 macrophage polarization plays a critical role. Nevertheless, the upstream signals that regulate this polarization—particularly specific instructions mediated via the “gut-muscle axis”—remain poorly defined. METHODS: The study was conducted as follows. First, intestinal barrier integrity following skeletal muscle contusion was assessed using histochemical staining and molecular assays. To elucidate the role of the gut microbiota in skeletal muscle repair, dysbiosis models and fecal microbiota transplantation (FMT) were established. Key gut microbiota and metabolites were subsequently identified through 16S rDNA sequencing and untargeted metabolomics analysis of fecal and serum samples. Based on these findings, targeted metabolite intervention experiments were conducted to evaluate their effects on the repair process of skeletal muscle contusion. To delineate the role of macrophages in this context, macrophage depletion was achieved via administration of clodronate liposomes. The impact of the key metabolites on macrophage polarization was then tested both in vivo and in vitro and the subsequent effect of polarized macrophages on C2C12 myoblast differentiation was examined in co-culture system. Finally, we explored the underlying epigenetic mechanisms through which the important metabolites regulates macrophage pol...