{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T05:19:34Z","timestamp":1790399974135,"version":"4.1.0"},"reference-count":63,"publisher":"American Association for the Advancement of Science (AAAS)","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82174527"],"award-info":[{"award-number":["82174527"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Project of First-Class Universities and High-level Dual Discipline for Guangzhou University of Chinese Medicine"}],"content-domain":{"domain":["spj.science.org"],"crossmark-restriction":true},"short-container-title":["Research"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:p>\n            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 (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            = 25) and sham-acupuncture (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            = 23) groups. After 8 weeks of intervention, 84% of patients in the acupuncture group achieved \u226520% reduction in methadone dosage, compared to 39% in the sham-acupuncture group (\n            <jats:italic toggle=\"yes\">P<\/jats:italic>\n            &lt; 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\n            <jats:italic toggle=\"yes\">Bilophila<\/jats:italic>\n            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\u00a0vitro experiments using THP-1 monocytes treated with cholic acid. The results showed that bile acid exposure suppressed galectin-9 and IFN-\u03b3 expression, while low-dose bile acid (simulating acupuncture effects) partially reversed this effect. These findings support a bile acid\u2013galectin\u2013interferon 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.\n          <\/jats:p>","DOI":"10.34133\/research.0741","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T05:07:23Z","timestamp":1748322443000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark_01","source":"Crossref","is-referenced-by-count":9,"title":["Single-Cell RNA Transcriptomics and Multi-omics Analyses Reveal the Clinical Effects of Acupuncture on Methadone Reduction"],"prefix":"10.34133","volume":"8","author":[{"given":"Yiming","family":"Chen","sequence":"first","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baochao","family":"Fan","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingchun","family":"Zeng","sequence":"additional","affiliation":[{"name":"Department of Acupuncture, \rFirst Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutian","family":"Zou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, \rSun Yat-Sen University Cancer Center, Guangzhou, China."},{"name":"Dana-Farber Cancer Institute, \rHarvard Medical School, Boston, MA 02215, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyang","family":"Tao","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."},{"name":"Jiangsu Medical College","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peiming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."},{"name":"The Eighth Clinical College of Medicine, \rGuangzhou University of Chinese Medicine, Foshan, Guangdong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Liang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, State Key Laboratory of Traditional Chinese Medicine Syndrome, \rGuangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangfang","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Neurology, \rMayo Clinic, Rochester, MN 55905, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailin","family":"Tang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, \rSun Yat-Sen University Cancer Center, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7821-4699","authenticated-orcid":true,"given":"Liming","family":"Lu","sequence":"additional","affiliation":[{"name":"Clinical Research and Big Data Laboratory, South China Research Center for Acupuncture and Moxibustion, Medical College of Acu-Moxi and Rehabilitation, \rGuangzhou University of Chinese Medicine, Guangzhou, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","published-online":{"date-parts":[[2025,6,24]]},"reference":[{"key":"e_1_3_4_2_2","volume-title":"WHO drug information","author":"World Health Organization","year":"2024","unstructured":"World Health Organization. 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