# Acupuncture for Major Depressive Disorder: Exploring the Gut Microbiota as a Novel Therapeutic Pathway

## TL;DR

Acupuncture at specific points can reduce depression-like behaviors in mice by changing gut bacteria and boosting a key brain-acting metabolite.

## Contribution

This study reveals a novel mechanism by which acupuncture alleviates depression through modulation of gut microbiota and associated metabolic pathways.

## Key findings

- Acupuncture reduced depression-like behaviors in stressed mice, restoring sucrose preference and reducing immobility in the tail suspension test.
- Acupuncture increased beneficial gut bacteria and decreased pathogenic Clostridium sp. A3LF 105b, while elevating the metabolite sphinganine 1-phosphate (S1P).
- S1P activation of the neuroactive ligand–receptor interaction pathway restored neuronal activity and alleviated depressive symptoms.

## Abstract

This study investigates the efficacy of acupuncture at Baihui (GV20) and Zusanli (ST36) acupoints in alleviating depressive symptoms and elucidates the underlying mechanisms.

Sixty male C57BL/6J mice were subjected to an 8‐week chronic unpredictable mild stress (CUMS) paradigm. Acupuncture was administered to two groups during the final 3 weeks: one under CUMS and the other without stress. Behavioral assessments, including the sucrose preference test and tail suspension test (TST), evaluated depression‐like behaviors. 16S rRNA sequencing and non‐targeted metabolomics analyzed gut microbiota and metabolites, respectively, with association analysis exploring the mechanistic pathways.

Acupuncture significantly ameliorated CUMS‐induced depression‐like behaviors, restoring sucrose preference (from a significant reduction in CUMS, p < 0.001, to an increase in CUMS + AP, p = 0.035) and reducing immobility time in the TST (p = 0.045). 16S rRNA sequencing revealed that acupuncture partially restored the CUMS‐disrupted Bacteroidetes/Firmicutes ratio by specifically decreasing the pathobiont Clostridium sp. A3LF 105b and increasing beneficial bacteria such as Faecalibacterium and Lachnospiraceae UCG 001. These microbial shifts were functionally linked to the elevation of the critical metabolite sphinganine 1‐phosphate (S1P). Spearman correlation analysis revealed a negative correlation between Clostridium sp. A3LF 105b and S1P (p < 0.01, R < −0.52). The modulation of gut microbiota led to increased S1P, which in turn activated the “neuroactive ligand–receptor interaction” pathway, thereby restoring neuronal activity and alleviating depressive behavior.

The study underscores the potential of acupuncture as an antidepressant treatment, highlighting its impact on gut microbiota and metabolic pathways in alleviating depressive symptoms.

Acupuncture at GV20 and ST36 alleviates depression by modulating gut microbiota, increasing beneficial bacteria, and enhancing neuroactive metabolites like Sphinganine 1‐phosphate, thereby restoring neuronal activity and reducing depressive behaviors.