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Peer-reviewedCC BY 4.0Frontiers in Immunology

Low-frequency passive mechanical stimulation produces antidepressant-like effects in rats involving gut–brain axis modulation

  • Rong Gao1,2
  • Wenjing Pu1,2
  • Yifei Lv1,2
  • Liqiong Liu1
  • Yan Zhao3
  • Hao Liu4
  • Li Chen1,2
  • Nan Guan5
  • Hongen Li1,2
5 affiliations
  1. 1School of Basic Medicine, Gansu Medical College, Pingliang, China
  2. 2Key Laboratory of Microbial Cohort and Multi-omics Research in Gansu Province, Gansu Medical College, Pingliang, China
  3. 3Pingliang Mental Health Center, Pingliang, China
  4. 4School of Clinical Medicine, Gansu Medical College, Pingliang, China
  5. 5Affiliated Hospital of Gansu Medical College, Pingliang, China
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Abstract

Introduction: Depression is associated with dysregulation of neuroendocrine, immune, and gut -brain axis pathways. Exercise is an effective non-pharmacological intervention; however, poor motivation and fatigue limit adherence in patients with depression.

Methods: We investigated a novel passive exercise modality, low-frequency passive vertical oscillation assisted by elastic ropes (LF-PVO-ER), in a chronic unpredictable mild stress (CUMS) rat model.

Results: LF-PVO-ER significantly improved depressive-like behaviors, including anhedonia and behavioral despair. Alongside these behavioral improvements, increases were observed in serum serotonin and brain-derived neurotrophic factor (BDNF), along with reductions in serum corticosterone, inflammatory markers (IL-6, TNF), and lipopolysaccharide (LPS). Histological analysis revealed attenuation of hippocampal and colonic injury. 16S rRNA sequencing showed partial restoration of CUMS-induced gut microbiota dysbiosis, as reflected by increased diversity and enrichment of short-chain fatty acid (SCFA)-associated genera. Untargeted metabolomics revealed changes in amino acid, lipid, and bile acid metabolism. Integrated analyses indicated coordinated associations among gut microbiota, metabolites, and neuroimmune markers.

Conclusion: These findings suggest that LF-PVO-ER may exert antidepressant-like effects through multiple pathways involving neuroendocrine function, inflammatory responses, and gut microbiota -metabolite interactions, supporting its potential as a passive exercise strategy for depression intervention.

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Cite

BibTeXRIS
BibTeX
@article{gao2026lowfrequency,
  title = {{Low-frequency passive mechanical stimulation produces antidepressant-like effects in rats involving gut–brain axis modulation}},
  author = {Rong Gao and Wenjing Pu and Yifei Lv and Liqiong Liu and Yan Zhao and Hao Liu and Li Chen and Nan Guan and Hongen Li},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1928978},
  url = {https://doi.org/10.3389/fimmu.2026.1928978},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Low-frequency passive mechanical stimulation produces antidepressant-like effects in rats involving gut–brain axis modulation
AU  - Rong Gao
AU  - Wenjing Pu
AU  - Yifei Lv
AU  - Liqiong Liu
AU  - Yan Zhao
AU  - Hao Liu
AU  - Li Chen
AU  - Nan Guan
AU  - Hongen Li
PY  - 2026
DA  - 2026/10/12
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1928978
UR  - https://doi.org/10.3389/fimmu.2026.1928978
AB  - Introduction: Depression is associated with dysregulation of neuroendocrine, immune, and gut -brain axis pathways. Exercise is an effective non-pharmacological intervention; however, poor motivation and fatigue limit adherence in patients with depression.  Methods: We investigated a novel passive exercise modality, low-frequency passive vertical oscillation assisted by elastic ropes (LF-PVO-ER), in a chronic unpredictable mild stress (CUMS) rat model.  Results: LF-PVO-ER significantly improved depressive-like behaviors, including anhedonia and behavioral despair. Alongside these behavioral improvements, increases were observed in serum serotonin and brain-derived neurotrophic factor (BDNF), along with reductions in serum corticosterone, inflammatory markers (IL-6, TNF), and lipopolysaccharide (LPS). Histological analysis revealed attenuation of hippocampal and colonic injury. 16S rRNA sequencing showed partial restoration of CUMS-induced gut microbiota dysbiosis, as reflected by increased diversity and enrichment of short-chain fatty acid (SCFA)-associated genera. Untargeted metabolomics revealed changes in amino acid, lipid, and bile acid metabolism. Integrated analyses indicated coordinated associations among gut microbiota, metabolites, and neuroimmune markers.  Conclusion: These findings suggest that LF-PVO-ER may exert antidepressant-like effects through multiple pathways involving neuroendocrine function, inflammatory responses, and gut microbiota -metabolite interactions, supporting its potential as a passive exercise strategy for depression intervention.
SN  - 1664-3224
ER  -