Work

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

Year: 2026

Type: article

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.

Source: Frontiers in Immunology

DOI: 10.3389/fimmu.2026.1928978