Molecular mechanisms, evidence, and translational prospects of butyric acid in sarcopenia: a focus on the gut-muscle axis

doi:10.3969/j.issn.1674-8115.2026.10.013

Abstract

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

CLC Number:

R592

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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References 58

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