ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Electroacupuncture Alleviates Comorbid Obesity and Depression via the Gut-Brain Axis: Orchestrating SCFA-Producing Bacteria and Hippocampal Synaptic Plasticity
Yaxin Zhang 1
Yuxin Pang 1
HaoYuan Tan 1
Ronghui Xian 1
Junquan Liang 1
Qianyi Wen 1
Zhongxian Li 1
Luda Yan 1
Zeping Xie 2
Jingjing Li 1
Wenbin Fu 1
Zhou Peng 1
1. Guangzhou University of Chinese Medicine, Guangzhou, China
2. Chinese Academy of Sciences Shenzhen Institute of Advanced Technology, Shenzhen, China
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Abstract
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. 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. 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. 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.
Summary
Keywords
Depression, Electroacupuncture, gut-brain axis, Obesity, synaptic plasticity
Received
21 December 2025
Accepted
16 February 2026
Copyright
© 2026 Zhang, Pang, Tan, Xian, Liang, Wen, Li, Yan, Xie, Li, Fu and Peng. 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) or licensor 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.
*Correspondence: Yaxin Zhang
Disclaimer
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