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

作者：Jingyu Zeng, Li Meng, Zhuoran You, Jianguo Li, Simin Yan, Muhammad Shahzad Aslam, Junliang Shen, Peng Li, Yanyan Lin, Jingxuan Li, Hui Fang, Liu Ning, Yanbei Zhan, Shuqiong Huang, Tiansheng Zhang, Xianjun Meng · 发表于：Brain Research Bulletin · 年份：2025 · DOI：10.1016/j.brainresbull.2025.111590 · 被引用次数：4 · 研究领域：Acupuncture Treatment Research Studies、Gut microbiota and health、Tryptophan and brain disorders

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 behavi...