Gut-muscle axis crosstalk in age-related sarcopenia - mechanisms and therapeutic targets

Sep 28, 2026

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Gut-muscle axis crosstalk links intestinal dysbiosis with age-related sarcopenia through bidirectional interactions between gut microbiota, metabolites, and skeletal muscle signaling. Sarcopenia is a progressive decline in muscle mass, strength, and function that worsens quality of life and increases risks such as falls, frailty, hospitalization, and mortality. Gut microbiota influences muscle protein metabolism via metabolic products, including amino acids, lipopolysaccharides, and short-chain fatty acids, while skeletal muscle myokines regulate microbial diversity and composition, forming a dysbiosis-sarcopenia vicious cycle. This review integrates current mechanistic evidence and summarizes management strategies and therapeutic targets.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages20

Reading Time50 min

AccessFree to download

Introduction

Sarcopenia and clinical significance

Gut microbiota as an extrinsic regulator

Gut microbiota and host crosstalk

Microbial ecosystem and variability

Dominant taxa and health relevance

TYPE Review PUBLISHED 17 December 2025 DOI 10.3389/fmicb.2025.1638880 OPEN ACCESS EDITED BY Zhi Liu, Huazhong University of Science and Technology, China REVIEWED BY Kamal Awad, The University of Texas at Arlington, United States Yao Wei Zhang, Southern Medical University, China *CORRESPONDENCE Xiao-Dong Feng [fxd0502@163.com](fxd0502@163.com)[ ](fxd0502@163.com)Jing Gao [gaojing_9303@163.com](gaojing_9303@163.com) RECEIVED 31 May 2025 REVISED 26 November 2025 ACCEPTED 28 November 2025 PUBLISHED 17 December 2025 CITATION Gao LL, Chen Y, Dai T, Zheng J, Su SS, Chen YX, Chen LD, Gao J and Feng XD (2025) Gut-muscle axis crosstalk in age-related sarcopenia: mechanisms and therapeutic targets. Front. Microbiol. 16:1638880 . doi: 10.3389/fmicb.2025.1638880 COPYRIGHT © 2025 Gao, Chen, Dai, Zheng, Su, Chen, Chen, Gao and Feng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Gut-muscle axis crosstalk in age-related sarcopenia: mechanisms and therapeutic targets Ling-Li Gao1,2 , Yan Chen1 , Ting Dai1 , Jie Zheng2 , Shuo-Shuo Su2 , Yi-Xun Chen2 , Li-Dian Chen2 , Jing Gao1* and Xiao-Dong Feng1* 1 Department of Rehabilitation, The First Afﬁliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China, 2 School of Rehabilitation Medicine, Henan University of Chinese Medicine, Zhengzhou, China The interplay between gut microbiota and sarcopenia has emerged as a cutting-edge research topic in the medical ﬁeld, garnering signiﬁcant attention. Sarcopenia is an age-related syndrome characterized by a progressive decline in skeletal muscle mass, strength, and function, which profoundly impacts the quality of life in older adults and imposes substantial socioeconomic burdenson many counties. Accumulating evidence indicates that alterations in the gut microbiota are not only linked to various intestinal disorders but also to agingassociated conditions, such as sarcopenia. The gut microbiota plays a pivotal role in regulating skeletal muscle homeostasis via its metabolic products and is increasingly recognized as a potential pathophysiological factor contributing to sarcopenia development. Skeletal muscle, functioning as both a motor and endocrine organ, secretes myokines that exert critical regulatory effects on the gut microbiota. In sarcopenic individuals, reduced secretion of myokines correlates with decreased microbial diversity and compositional shifts, marked by diminished beneﬁcial microbes and increased potentially harmful species. This establishes a vicious cycle of gut dysbiosis-sarcopenia-gut dysbiosis. Modulation of the gut microbiota has been demonstrated to enhance muscle mass and function in elderly patients with sarcopenia. Metabolites derived from the gut microbiota, such as amino acids, lipopolysaccharides, and short-chain fatty acids, are known to modulate skeletal muscle protein metabolism by inﬂuencing anabolic and catabolic pathways. Nevertheless, the bidirectional mechanisms underlying the relationship between gut microbiota and agerelated sarcopenia remain incompletely understood. In this review, we aim to: (1) integrate current knowledge regarding the bidirectional interaction between sarcopenia and gut microbiota; (2) summarize existing management strategies for age-related sarcopenia based on this interaction. KEYWORDS gut-muscle axis, crosstalk, age-related sarcopenia, inﬂammation, microbial metabolites, neuroendocrine system, myokines, therapeutic targets Frontiers in Microbiology 01 [frontiersin.org](frontiersin.org) 1 Introduction Sarcop

FAQs

What is the gut-muscle axis in age-related sarcopenia?

The gut-muscle axis refers to bidirectional interactions between gut microbiota and skeletal muscle that can contribute to sarcopenia pathogenesis. Gut dysbiosis can affect muscle homeostasis, while muscle-derived myokines can modulate the microbiota.

How do gut microbiota metabolites influence skeletal muscle?

Microbiota-derived metabolites such as amino acids, lipopolysaccharides, and short-chain fatty acids modulate skeletal muscle protein metabolism. They do so by influencing anabolic and catabolic pathways.

What role do myokines play in the gut dysbiosis–sarcopenia cycle?

In sarcopenic individuals, reduced secretion of myokines is associated with decreased microbial diversity and compositional shifts. This can increase harmful species and contribute to a vicious cycle of gut dysbiosis and sarcopenia.

Sep 28, 2026

Uploaded by SANS