Does the Microbiota-Gut-Brain Axis Mediate the Antidepressant Effects of Acupuncture? A Structured Review of Preclinical and Clinical Evidence.

BACKGROUND: Acupuncture is used for depressive disorders, but the extent to which its effects are mediated by the microbiota-gut-brain axis (MGBA) remains uncertain. OBJECTIVE: To determine whether current preclinical and clinical evidence supports gut microbiota as a mediator, amplifier, or biomarker of acupuncture-related antidepressant effects. METHODS: Eight databases were searched from inception to 6 July 2026 for peer-reviewed studies of acupuncture in depressive disorders or validated depressive-like phenotypes that reported gut microbiota or microbiota-derived metabolite outcomes. RESULTS: Twenty-six independent studies were included: 22 preclinical and 4 clinical studies. Animal experiments consistently showed acupuncture-induced behavioral improvements accompanied by shifts in gut microbial composition, with several studies also documenting changes in intestinal barrier function, inflammatory signaling, microbial metabolites, neuroendocrine indicators, and synaptic plasticity. However, reported alterations at the phylum and taxon levels were inconsistent, and most work merely identified parallel changes instead of establishing microbiota mediation. One electroacupuncture donor fecal microbiota transplantation study offered the strongest evidence that acupuncture-remodeled microbiota can transfer behavioral benefits, while a second bidirectional transplantation confirmed microbiota participation in the disease model but could not establish acupuncture-specific microbiota mediation. Clinical evidence was limited to postpartum and post-stroke depression and was constrained by nonrandomized allocation, add-on designs, incomplete longitudinal microbiota sampling, and confounding. CONCLUSION: Current evidence supports a host-mediated ecological framework whereby acupuncture remodels the intestinal niche and modulates MGBA signaling. Nonetheless, microbiota-mediated effects have not been verified across most preclinical models and remain unconfirmed in clinical settings.