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

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

METHODS

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.

RESULTS

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.

CONCLUSION

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