{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:39:53Z","timestamp":1792197593457,"version":"4.4.0"},"reference-count":60,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82374564"],"award-info":[{"award-number":["82374564"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81873380"],"award-info":[{"award-number":["81873380"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82074566"],"award-info":[{"award-number":["82074566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Hubei Provincial Joint Fund Project","award":["2025AFD596"],"award-info":[{"award-number":["2025AFD596"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background: Alzheimer\u2019s disease (AD) lacks effective therapeutic strategies. Electroacupuncture (EA) offers promising neuroprotective effects, but its underlying mechanisms remain unclear. Objective: To explore the mechanisms of EA\u2019s neuroprotective effects on AD via microbiome and metabolome integration. Methods: Utilizing a well-established model of AD, Senescence-Accelerated Mouse Prone 8 (SAMP8), EA intervention was performed. 16S ribosomal RNA (rRNA) sequencing and serum metabolomics were conducted on SAMP8 mice, SAMP8 mice after EA intervention, and their normal control group Senescence-Accelerated Mouse Resistant 1 (SAMR1) mice. Results: SAMP8 mice were subjected to electroacupuncture (EA) treatment at the Baihui (GV20) and Shenshu (BL23) acupoints for 15 min daily over a period of four weeks. EA enhanced cognitive function and reduced neuronal damage in AD models. The treatment lowered pro-inflammatory cytokines (TNF-\u03b1, IL-1\u03b2) and AD-related pathologies (tau, A\u03b21-42). EA also rebalanced gut microbiota by increasing beneficial Gastranaerophilales while decreasing harmful Proteobacteria. Additionally, it restored purine and phenylpropanoid metabolism by regulating key metabolites. Importantly, EA reduced levels of specific metabolites linked to pro-inflammatory bacteria (Sphingomonas, Massilia, Escherichia-Shigella), simultaneously decreasing their abundance. These findings highlight EA\u2019s multi-target effects on neuroinflammation, gut microbiota, and metabolic pathways in AD. Notably, the interactions between EA-regulated key metabolites and AD-related targets, predicted via PubChem and ChEMBL databases, remain computational and have not been validated by experimental studies. Conclusions: EA exerts neuroprotective effects in AD via modulation of gut microbiota and metabolic pathways, representing a novel non-pharmacological therapeutic strategy.<\/jats:p>","DOI":"10.3390\/biom15111486","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T08:41:08Z","timestamp":1761122468000},"page":"1486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multi-Omics Integration Reveals Electroacupuncture Ameliorates Cognitive Impairment in Alzheimer\u2019s Disease via Gut\u2013Brain Axis"],"prefix":"10.3390","volume":"15","author":[{"given":"Shuai","family":"Zhang","sequence":"first","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyu","family":"Xu","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weixian","family":"Li","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Song","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pathology and Pathophysiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430074, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-9077","authenticated-orcid":false,"given":"Yanjun","family":"Du","sequence":"additional","affiliation":[{"name":"College of Acupuncture-Moxibustion and Orthopaedics, Hubei University of Chinese Medicine, Wuhan 430061, China"},{"name":"Hubei International Science and Technology Cooperation Base of Preventive Treatment by Acupuncture and Moxibustion, Wuhan 430061, China"},{"name":"Hubei Shizhen Laboratory, Wuhan 430061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41392-024-01911-3","article-title":"Recent advances in Alzheimer\u2019s disease: Mechanisms, clinical trials and new drug development strategies","volume":"9","author":"Zhang","year":"2024","journal-title":"Signal Transduct. 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