Electroacupuncture alleviates comorbid obesity and depression via the gut-brain axis: orchestrating SCFA-producing bacteria and hippocampal synaptic plasticity.

Overview

1. Shenzhen Bao'an Traditional Chinese Medicine Hospital, The Seventh Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China
2. Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China
3. Guangdong Provincial Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China

Abstract

Introduction: Comorbid obesity and depression (COMBD) represents a complex metabolic-neuropsychiatric challenge with limited therapeutic options. While Electroacupuncture (EA) is effective for both metabolic and mood disorders, the systemic mechanisms—particularly the interplay between the gut microbiome and hippocampal plasticity—remain elusive.

Methods: We established a COMBD rat model using a high-fat diet combined with chronic unpredictable mild stress (CUMS). An integrated multi-omics approach comprising 16S rDNA sequencing, LC-MS/MS serum metabolomics, and hippocampal transcriptomics was utilized to decipher the therapeutic mechanisms of EA.

Results: EA treatment significantly attenuated body weight gain and reversed depressive-like behaviors. Crucially, EA restructured the dysbiotic gut microbiota, specifically increasing the abundance of short-chain fatty acid (SCFA)-producing bacteria. This microbial restoration was strongly correlated with a reprogrammed serum metabolic profile. In the hippocampus, transcriptomic analysis identified Cd74 as a pivotal upstream regulator modulated by EA. Furthermore, EA mitigated hippocampal oxidative stress and restored synaptic plasticity, evidenced by increased dendritic spine density and upregulated synaptic protein expression.

Conclusion: Our findings suggest that EA ameliorates COMBD via a coordinated “Microbiota-Metabolism-Brain” axis. Specifically, EA creates a neuroprotective milieu by promoting beneficial SCFA-producing bacteria and regulating metabolic signals, which subsequently targets hippocampal Cd74 to restore synaptic plasticity. This study provides a novel mechanistic basis for the clinical application of EA in treating complex metabolic-mood comorbidities.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• bioproject:PRJNA1423444, at NCBI BioProject; found in “Data availability statement”

Data availability statement

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found at: NCBI BioProject PRJNA1423444 (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1423444).

Reproduced under the paper's license (CC BY), from the paper cited above.

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Recorded: type, language, journal, volume, pages, dates, 12 authors, 5 keywords, 2 funders, 39 references.

Cite

This paper

Zhang, Y., Pang, Y., Tan, H., Xian, R., Liang, J., Wen, Q., Li, Z., Yan, L., Xie, Z., Li, J., Fu, W., & Zhou, P. (2026). Electroacupuncture alleviates comorbid obesity and depression via the gut-brain axis: orchestrating SCFA-producing bacteria and hippocampal synaptic plasticity. Frontiers in microbiology, 17, 1772788. https://doi.org/10.3389/fmicb.2026.1772788

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