Chen Yiming, Fan Baochao, Zeng Jingchun, Zou Yutian, Tao Chenyang, Chen Chen, Zhang Peiming, Liang Jian, Qi Fangfang, Tang Hailin, Lu Liming
Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Acupuncture, First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Research (Wash D C). 2025 Jun 24;8:0741. doi: 10.34133/research.0741. eCollection 2025.
Opioid use disorders (OUDs) pose a substantial global health burden, with methadone maintenance treatment (MMT) widely adopted as an intervention; however, MMT is associated with immunosuppression, metabolic disturbances, and dysbiosis of the gut microbiota. Despite the potential of acupuncture in reducing methadone dosages and opioid addiction, the underlying biological mechanisms remain unclear. Therefore, we aimed to integrate clinical trial data with multi-omics analysis, including single-cell sequencing, transcriptomics, metabolomics, and metagenomics, to evaluate the effects of acupuncture in patients undergoing MMT. We collected peripheral blood mononuclear cells, plasma, and fecal samples from 48 MMT participants in a randomized, placebo-controlled trial. Participants were divided into acupuncture ( = 25) and sham-acupuncture ( = 23) groups. After 8 weeks of intervention, 84% of patients in the acupuncture group achieved ≥20% reduction in methadone dosage, compared to 39% in the sham-acupuncture group ( < 0.01). Our findings revealed that acupuncture may activate the defense response to viruses, with altered immune cell functions in classical monocytes correlating with clinical responses to reduced methadone doses. Acupuncture might ameliorate intestinal microbial disruptions caused by OUD by up-regulating and modulating bile acid metabolism. Furthermore, acupuncture up-regulated galectin-9 (LGALS9)-mediated intercellular communication between classical monocytes and other immune subsets. To further validate the mechanistic link between bile acid metabolism and immune regulation, we conducted in vitro experiments using THP-1 monocytes treated with cholic acid. The results showed that bile acid exposure suppressed galectin-9 and IFN-γ expression, while low-dose bile acid (simulating acupuncture effects) partially reversed this effect. These findings support a bile acid-galectin-interferon axis that may be modulated by acupuncture in OUD. Collectively, our results provide clinical and mechanistic evidence supporting acupuncture as a potential adjunct therapy to mitigate the adverse effects of long-term opioid use.
阿片类物质使用障碍（OUDs）给全球带来了沉重的健康负担，美沙酮维持治疗（MMT）作为一种干预措施被广泛采用；然而，MMT与免疫抑制、代谢紊乱以及肠道微生物群失调有关。尽管针灸在减少美沙酮剂量和阿片类物质成瘾方面具有潜力，但其潜在的生物学机制仍不清楚。因此，我们旨在将临床试验数据与多组学分析相结合，包括单细胞测序、转录组学、代谢组学和宏基因组学，以评估针灸对接受MMT治疗的患者的影响。我们在一项随机、安慰剂对照试验中，收集了48名接受MMT治疗的参与者的外周血单核细胞、血浆和粪便样本。参与者被分为针灸组（n = 25）和假针灸组（n = 23）。经过8周的干预，针灸组84%的患者美沙酮剂量减少了≥20%，而假针灸组为39%（P < 0.01）。我们的研究结果表明，针灸可能激活对病毒的防御反应，经典单核细胞中免疫细胞功能的改变与美沙酮剂量减少的临床反应相关。针灸可能通过上调FXR并调节胆汁酸代谢来改善由OUD引起的肠道微生物紊乱。此外，针灸上调了半乳糖凝集素-9（LGALS9）介导的经典单核细胞与其他免疫亚群之间的细胞间通讯。为了进一步验证胆汁酸代谢与免疫调节之间的机制联系，我们使用经胆酸处理的THP-1单核细胞进行了体外实验。结果表明，胆汁酸暴露会抑制半乳糖凝集素-9和IFN-γ的表达，而低剂量胆汁酸（模拟针灸效果）可部分逆转这种效应。这些发现支持了一个可能由针灸在OUD中调节的胆汁酸-半乳糖凝集素-干扰素轴。总体而言，我们的结果提供了临床和机制证据，支持针灸作为一种潜在的辅助治疗方法，以减轻长期使用阿片类物质的不良反应。
