Microecological-metabolic links along the brain-gut-muscle axis in Tuina analgesia from the perspectives of gut metagenomics and untargeted metabolomics
5 affiliations
- 1Department of Tuina, Affiliated Hospital of Changchun University of Chinese Medicine
- 2Department of Thyroid Breast Surgery, Affiliated Hospital of Changchun University of Traditional Chinese Medicine
- 3Acupuncture and Tuina College, Changchun University of Chinese Medicine
- 4Department of Massage, Hangzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medical University
- 5Department of Tuina, Affiliated Hospital of Changchun University of Traditional Chinese Medicine
Abstract
Chronic pain involves multilevel processes including central sensitization, peripheral tissue abnormalities, neuroimmune responses, metabolic alterations, and changes in gut microecology. Tuina and related manual therapies can influence local soft-tissue status, peripheral sensory input, autonomic activity, inflammatory responses, and muscle metabolism, whereas the links between their distal systemic effects and gut microecology remain insufficiently characterized. The brain, gut, and skeletal muscle can interact through autonomic pathways, immune-inflammatory signaling, circulating metabolites, myokines, and other distal signals, providing a biological context for analyzing cross-organ changes related to Tuina analgesia. A limited number of studies have reported changes in gut microbiota after Tuina, massage, or combined manual interventions; however, direct evidence continuously linking mechanical stimulation, microbial function, metabolic signaling, and pain improvement remains limited. Gut metagenomics extends analysis beyond species composition to strains, functional genes, and metabolic pathway potential, whereas untargeted metabolomics captures metabolic changes jointly shaped by the host and microbiota. Short-chain fatty acids, bile acids, tryptophan derivatives, and molecules related to lipid and energy metabolism have shown functional associations with neuroimmune regulation, sensory neural activity, and pain sensitization in different pain models. Myokines, metabolites, and extracellular vesicle signals derived from skeletal muscle also provide a possible biological basis for bidirectional gut-muscle communication. Nevertheless, most of these mechanisms originate from studies of pain, the microbiome, or exercise physiology and cannot be directly equated with mechanisms of Tuina analgesia. Integrated metagenomic and metabolomic analyses can identify candidate links involving microbial functions, metabolic alterations, host responses, and pain phenotypes, thereby narrowing the scope of subsequent functional validation. Their interpretation remains influenced by Tuina stimulation parameters, diet, gut transit, medication use, circadian rhythms, and other host factors. Standardization of the intervention, longitudinal multi-omics observation, targeted quantification, functional experiments, and cross-center replication will help clarify the temporal relationships and functional significance of these changes. Microecological-metabolic links across the brain, gut, and skeletal muscle can therefore serve as a cross-organ framework for investigating the systemic effects of Tuina analgesia, although specific pathways and their clinical predictive value still require direct experimental and prospective validation.
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BibTeX
@article{zhang2026microecologicalmetabolic,
title = {{Microecological-metabolic links along the brain-gut-muscle axis in Tuina analgesia from the perspectives of gut metagenomics and untargeted metabolomics}},
author = {Xinlu Zhang and Huan Wang and Jie Xing and Hailong Zhao and Yangshengjie Liu and Jundong Jiao},
journal = {Frontiers in Microbiology},
year = {2026},
month = oct,
doi = {10.3389/fmicb.2026.1957609},
url = {https://www.frontiersin.org/articles/10.3389/fmicb.2026.1957609/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Microecological-metabolic links along the brain-gut-muscle axis in Tuina analgesia from the perspectives of gut metagenomics and untargeted metabolomics
AU - Xinlu Zhang
AU - Huan Wang
AU - Jie Xing
AU - Hailong Zhao
AU - Yangshengjie Liu
AU - Jundong Jiao
PY - 2026
DA - 2026/10/23
JO - Frontiers in Microbiology
DO - 10.3389/fmicb.2026.1957609
UR - https://www.frontiersin.org/articles/10.3389/fmicb.2026.1957609/full
AB - Chronic pain involves multilevel processes including central sensitization, peripheral tissue abnormalities, neuroimmune responses, metabolic alterations, and changes in gut microecology. Tuina and related manual therapies can influence local soft-tissue status, peripheral sensory input, autonomic activity, inflammatory responses, and muscle metabolism, whereas the links between their distal systemic effects and gut microecology remain insufficiently characterized. The brain, gut, and skeletal muscle can interact through autonomic pathways, immune-inflammatory signaling, circulating metabolites, myokines, and other distal signals, providing a biological context for analyzing cross-organ changes related to Tuina analgesia. A limited number of studies have reported changes in gut microbiota after Tuina, massage, or combined manual interventions; however, direct evidence continuously linking mechanical stimulation, microbial function, metabolic signaling, and pain improvement remains limited. Gut metagenomics extends analysis beyond species composition to strains, functional genes, and metabolic pathway potential, whereas untargeted metabolomics captures metabolic changes jointly shaped by the host and microbiota. Short-chain fatty acids, bile acids, tryptophan derivatives, and molecules related to lipid and energy metabolism have shown functional associations with neuroimmune regulation, sensory neural activity, and pain sensitization in different pain models. Myokines, metabolites, and extracellular vesicle signals derived from skeletal muscle also provide a possible biological basis for bidirectional gut-muscle communication. Nevertheless, most of these mechanisms originate from studies of pain, the microbiome, or exercise physiology and cannot be directly equated with mechanisms of Tuina analgesia. Integrated metagenomic and metabolomic analyses can identify candidate links involving microbial functions, metabolic alterations, host responses, and pain phenotypes, thereby narrowing the scope of subsequent functional validation. Their interpretation remains influenced by Tuina stimulation parameters, diet, gut transit, medication use, circadian rhythms, and other host factors. Standardization of the intervention, longitudinal multi-omics observation, targeted quantification, functional experiments, and cross-center replication will help clarify the temporal relationships and functional significance of these changes. Microecological-metabolic links across the brain, gut, and skeletal muscle can therefore serve as a cross-organ framework for investigating the systemic effects of Tuina analgesia, although specific pathways and their clinical predictive value still require direct experimental and prospective validation.
SN - 1664-302X
ER -