丁酸在肌少症中的分子机制、证据与转化前景：聚焦肠-肌肉轴

doi:10.3969/j.issn.1674-8115.2026.10.013

摘要/Abstract

摘要：

肌少症是与年龄相关的进行性、全身性骨骼肌质量、力量及功能下降为特征的综合征，已成为全球公共卫生挑战之一。近年来，“肠-肌肉轴”理论的提出为解析肌少症病理机制提供了全新视角。肠道菌群代谢产物丁酸作为该轴介导远程通信的关键信号分子备受关注。该文系统综述了丁酸调控骨骼肌稳态的分子机制、临床证据及转化应用进展。在机制层面，丁酸通过多维路径发挥保护作用：①表观遗传：通过抑制组蛋白去乙酰化酶活性及下调特定组蛋白修饰水平，解除成肌基因抑制。②卫星细胞：通过单羧酸转运体1（monocarboxylate transporter 1，MCT1）维持卫星细胞静息态，并经丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）和Wnt信号通路支持其分化，共同维持卫星细胞稳态与再生潜能。③免疫代谢：既通过加固肠道屏障减轻系统性炎症，又作为G蛋白偶联受体的配体介导抗炎效应并增强线粒体功能，实现抑制降解与促进合成的双向调节。在临床与应用层面，多项研究证实产丁酸菌丰度下降与慢性病相关的肌肉流失密切相关。丁酸联合运动与蛋白质补充展现出显著的协同干预效应，相关标志物在肌少症筛查与预后评估中显示出潜在价值。丁酸对肌卫星细胞的调控存在剂量依赖的双向效应，且临床干预效果受个体基线菌群等异质性因素影响。未来需借助多组学技术界定不同病理状态下的有效治疗窗口，探索基于个体微生态特征的精准干预策略。

关键词: 肌少症, 短链脂肪酸, 丁酸, 肠-肌肉轴, 膳食纤维, 衰老

Abstract:

Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function, emerging as a significant global public health challenge. Recently, the "gut-muscle axis" theory has provided a novel perspective on its pathogenesis, with butyrate, a key microbial metabolite, garnering intensive focus as a critical signaling molecule mediating remote communication along this axis. This review systematically summarizes the molecular mechanisms of butyrate in skeletal muscle homeostasis, alongside clinical evidence and progress in translational applications. At the mechanistic level, butyrate exerts protective effects through multi-dimensional pathways: ①Epigenetically, it alleviates the repression of myogenic genes by inhibiting histone deacetylase (HDAC) activity and downregulating specific histone modifications. ②Regarding satellite cells, it maintains satellite cell quiescence through monocarboxylate transporter 1 (MCT1) and supports their differentiation via mitogen-activated protein kinase (MAPK) and Wnt signaling pathways, collectively preserving satellite cell homeostasis and regenerative potential. ③In terms of immuno-metabolism, butyrate fortifies the intestinal barrier to mitigate systemic inflammation and acts as a ligand for G protein-coupled receptors (GPRs), mediating anti-inflammatory effects and enhancing mitochondrial function to achieve dual regulation of protein degradation inhibition and synthesis promotion. At the clinical and translational levels, multiple studies have confirmed that decreased abundance of butyrate-producing bacteria is closely associated with muscle loss in chronic diseases. Furthermore, butyrate combined with exercise and protein supplementation shows significant synergistic effects, and related biomarkers hold potential value in screening and prognostic assessment of sarcopenia. However, butyrate's regulation of satellite cells exhibits a dose-dependent bidirectional effect, and its clinical efficacy is influenced by heterogeneous factors such as individual baseline microbiota. Future research should leverage multi-omics technologies to define therapeutic windows in various pathological states and explore precision intervention strategies tailored to individual microecological profiles.

Key words: sarcopenia, short-chain fatty acid, butyrate, gut-muscle axis, dietary fiber, aging

中图分类号:

R592

郭彤, 徐鑫. 丁酸在肌少症中的分子机制、证据与转化前景：聚焦肠-肌肉轴[J]. 上海交通大学学报（医学版）, 2026, 46(10): 1428-1434.

Guo Tong, Xu Xin. Molecular mechanisms, evidence, and translational prospects of butyric acid in sarcopenia: a focus on the gut-muscle axis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2026,(10): 1428-1434.

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