Acupuncture improves depression-like behaviors in rats through gut microbiota and TLR4/MyD88/NF-κB pathway modulation

Oct 23, 2025Brain research bulletin

Acupuncture reduces depression-like behaviors in rats by changing gut bacteria and immune signaling pathways

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Gut-Brain Axis on OpenScience ↗PubMed ↗DOI ↗

Abstract

Acupuncture increased sucrose preference to 89.61% and reduced immobility in the forced swim test to 20.52 seconds in rats subjected to chronic unpredictable mild stress.

Acupuncture alleviated depressive-like behaviors induced by chronic unpredictable mild stress in rats.
Colonic injury was reduced following acupuncture treatment.
Acupuncture helped restore the balance of gut microbiota, specifically the Firmicutes/Bacteroidetes ratio.
Inhibition of TLR4/MyD88/NF-κB signaling was observed in both the hypothalamus and colon.
Serum levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α decreased after acupuncture.
HPA-axis activity normalized with acupuncture treatment.

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BACKGROUND: Acupuncture (AP) is used for depression, but mechanisms remain unclear. We asked whether acupuncture attenuates chronic unpredictable mild stress (CUMS)-induced depressive-like behaviors in rats and, specifically, whether its efficacy is linked to remodeling gut microbiota and inhibiting TLR4/MyD88/NF-κB signaling along the gut-brain axis with concomitant rebalancing of hypothalamic-pituitary-adrenal (HPA) activity.

METHODS: Male Sprague-Dawley rats underwent CUMS with or without acupuncture. Sucrose preference test (SPT) and forced swim test (FST) assessed behavior. Colonic injury was scored after H&E staining; microbiota were profiled by 16S rDNA sequencing. TLR4/MyD88/NF-κB expression in hypothalamus and colon was measured by Western blot/Real-time PCR; Iba1 + microglia were quantified by immunofluorescence. Serum cytokines and HPA hormones were assayed by ELISA.

RESULTS: Acupuncture increased sucrose preference (89.61 ± 2.551 % vs. 73.82 ± 5.711 %, P < 0.05) and reduced FST immobility (20.52 ± 3.784 s vs. 46.13 ± 7.391 s, P < 0.01) versus untreated CUMS. It lowered colonic injury (P < 0.05) and partly restored the Firmicutes/Bacteroidetes ratio. TLR4/MyD88/NF-κB signaling was suppressed in the hypothalamus and colon (TLR4 protein -37 %, P < 0.05), with fewer Iba1 + microglia (27.3 ± 3.2 % vs. 45.6 ± 4.8 %, P < 0.01). Serum IL-6, IL-1β, and TNF-α decreased, and HPA-axis activity normalized.

CONCLUSIONS: Acupuncture alleviates CUMS-induced depressive-like behaviors. The benefits are associated with gut microbiota remodeling, inhibition of TLR4/MyD88/NF-κB signaling, and stabilization of HPA-axis function, supporting an immune-microbiota-neuroendocrine mechanism.