Mechanistic Insights Into How Acupuncture Modulates Host Immunity via the Gut Microbiota‐Macrophage Axis
- 1Department of Laboratory Medicine Jiangsu Road Sub‐district Community Health Service Center Qingdao City Shandong Province China
- 2Department of Traditional Chinese Medicine Badaxia Sub‐district Community Health Service Center Qingdao City Shandong Province China
- 3Department of General Internal Medicine The Integrated Traditional Chinese and Western Medicine Hospital of Shinan District (The People's Hospital of Shinan District) Qingdao City Shandong Province China
Abstract
Background: Acupuncture is proposed to operate within the neuro‐endocrine‐immune network. Its therapeutic efficacy is proposed to be partly mediated through the gut microbiota‐macrophage axis. This proposal is based primarily on preclinical findings. This axis may act as a biological transducer that helps sustain systemic homeostasis1. This review synthesizes current evidence on how acupuncture may orchestrate a top‐down regulation of the intestinal microenvironment through somato‐vagal circuits, particularly those involving PROKR2‐expressing sensory fibers.
Materials and Methods: This narrative review examined recent preclinical and clinical literature on acupuncture, gut microbiota, metabolites, and macrophage polarization. Studies were selected by relevance and expert judgment. Evidence was organized around the proposed gut microbiota‐macrophage axis.
Results: In preclinical rodent models and some human studies, acupuncture has been reported to suppress pathogens such as Proteobacteria. It may also promote symbionts like Akkermansia muciniphila and butyrate‐producing taxa. Butyrate promotes anti‐inflammatory M2 macrophage polarization via histone deacetylase (HDAC) inhibition and G‐protein‐coupled receptor signaling. In rodent models, acupuncture has been shown to strengthen barrier integrity. It may upregulate tight junction proteins. It may also prevent lipopolysaccharide (LPS) translocation and suppress M1‐driven cascades. These effects extend distally via the gut‐lung and gut‐brain axes.
Discussion: It is important to note that this proposed cascade is primarily derived from preclinical rodent models, and direct evidence in humans that confirms all steps from vagal activation to macrophage reprogramming remains incomplete. Ultimately, acupuncture may serve as a potential eco‐immunological therapy that restores balance between the microbiome and innate immunity. This framework provides a preliminary conceptual basis for the eventual development of personalized, biomarker‐driven protocols for chronic inflammatory diseases, although this hypothesis requires rigorous causal validation.
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BibTeX
@article{yang2026mechanistic,
title = {{Mechanistic Insights Into How Acupuncture Modulates Host Immunity via the Gut Microbiota‐Macrophage Axis}},
author = {Tao Yang and Mei Li and Xiaowen Wu},
journal = {Immunity, Inflammation and Disease},
year = {2026},
month = nov,
doi = {10.1002/iid3.70567},
url = {https://doi.org/10.1002/iid3.70567},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanistic Insights Into How Acupuncture Modulates Host Immunity via the Gut Microbiota‐Macrophage Axis
AU - Tao Yang
AU - Mei Li
AU - Xiaowen Wu
PY - 2026
DA - 2026/11/05
JO - Immunity, Inflammation and Disease
DO - 10.1002/iid3.70567
UR - https://doi.org/10.1002/iid3.70567
AB - Background: Acupuncture is proposed to operate within the neuro‐endocrine‐immune network. Its therapeutic efficacy is proposed to be partly mediated through the gut microbiota‐macrophage axis. This proposal is based primarily on preclinical findings. This axis may act as a biological transducer that helps sustain systemic homeostasis1. This review synthesizes current evidence on how acupuncture may orchestrate a top‐down regulation of the intestinal microenvironment through somato‐vagal circuits, particularly those involving PROKR2‐expressing sensory fibers. Materials and Methods: This narrative review examined recent preclinical and clinical literature on acupuncture, gut microbiota, metabolites, and macrophage polarization. Studies were selected by relevance and expert judgment. Evidence was organized around the proposed gut microbiota‐macrophage axis. Results: In preclinical rodent models and some human studies, acupuncture has been reported to suppress pathogens such as Proteobacteria. It may also promote symbionts like Akkermansia muciniphila and butyrate‐producing taxa. Butyrate promotes anti‐inflammatory M2 macrophage polarization via histone deacetylase (HDAC) inhibition and G‐protein‐coupled receptor signaling. In rodent models, acupuncture has been shown to strengthen barrier integrity. It may upregulate tight junction proteins. It may also prevent lipopolysaccharide (LPS) translocation and suppress M1‐driven cascades. These effects extend distally via the gut‐lung and gut‐brain axes. Discussion: It is important to note that this proposed cascade is primarily derived from preclinical rodent models, and direct evidence in humans that confirms all steps from vagal activation to macrophage reprogramming remains incomplete. Ultimately, acupuncture may serve as a potential eco‐immunological therapy that restores balance between the microbiome and innate immunity. This framework provides a preliminary conceptual basis for the eventual development of personalized, biomarker‐driven protocols for chronic inflammatory diseases, although this hypothesis requires rigorous causal validation.
SN - 2050-4527
ER -