ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Microorganisms in Vertebrate Digestive Systems
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1576686
Transcutaneous auricular vagus nerve stimulation regulates gut microbiota mediated peripheral inflammation and metabolic disorders to suppress depressive-like behaviors in CUMS rats
Provisionally accepted
Xinjiang Zhang1
Xun He1
Yanan Zhao1
Qi Zou1Yulong Liang1
Jinling Zhang1Bowen Feng1
Peijing Rong2*
Yu Wang1*- 1Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China
- 2Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
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Depression is a common mental disorder, and the changes of intestinal microflora and peripheral plasma metabolites can affect the gut-brain axis through vagus nerve, leading to the occurrence and progress of the disease. Transcutaneous auricular vagus nerve stimulation (taVNS) has been previously shown to be clinically safe and effective in treating depression.However, there is no evidence whether its antidepressant effect is related to the regulation of intestinal flora and metabolites.In this study, we established a chronic unpredictable mild stress (CUMS) model in SD rats for 5 weeks. During the last 3 weeks of CUMS treatment, the rats received continuous taVNS intervention for 3 weeks.Depressive-like behavior in SD rats was evaluated through behavioral assessments. The gut microbiota and plasma were analyzed using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS) techniques.Behavioral tests showed that taVNS significantly reversed the depressive-like behavior induced by CUMS in rats.16S rRNA sequencing results showed that taVNS could improve the intestinal flora structure of CUMS rats.Microbial community characterization index showed that taVNS could reverse the gut microbiota dysbiosis in CUMS rats. ROC analysis revealed that Lachnospiraceae_NK4A136_group 、 Parabacteroides and Corynebacterium_1 are potential biomarkers for diagnosing gut microbiota dysbiosis in CUMS rats and could also serve as potential therapeutic targets for taVNS.Plasma metabolomics results showed that the differential metabolites between the CUMS group and the control group were primarily enriched in pathways such as bile acid metabolism, arachidonic acid metabolism, and ether lipid metabolism. The differential metabolites between the taVNS group and the CUMS group were primarily enriched
Keywords: Depression, Gut Microbiota, Metabolomics, brain-gut axis, Transcutaneous auricular vagus nerve stimulation
Received: 14 Feb 2025; Accepted: 13 Jun 2025.
Copyright: © 2025 Zhang, He, Zhao, Zou, Liang, Zhang, Feng, Rong and Wang. 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:
Peijing Rong, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
Yu Wang, Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, China
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