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Integr. Neurosci."],"abstract":"<jats:p>Mild cognitive impairment (MCI) represents a critical prodromal stage of Alzheimer\u2019s disease. This review synthesizes current evidence to present a coherent pathological cascade driving MCI progression: gut microbiota dysbiosis (e.g., enrichment of Prevotella and depletion of Akkermansia) triggers a butyrate deficit and compromise of intestinal integrity, leading to systemic inflammation. This inflammatory milieu upregulates indoleamine 2,3-dioxygenase 1 (IDO1), shifting tryptophan metabolism toward the kynurenine pathway and resulting in the dominance of neurotoxic branches (3-hydroxykynurenine [3-HK], quinolinic acid [QUIN]) over neuroprotective kynurenic acid (KYNA). This metabolic imbalance promotes N-methyl-D-aspartate (NMDA) receptor-mediated excitotoxicity, oxidative stress, and neuroinflammation, which collectively precipitate synaptic dysfunction and cognitive decline. We explicitly highlight this \u201cgut-immune-metabolic\u201d vicious cycle as the core framework of MCI pathology. Targeting this cycle through a dual strategy\u2014restoring microbial diversity and pharmacologically inhibiting the IDO1\/kynurenine 3-monooxygenase (KMO) enzymes\u2014represents a promising therapeutic approach to delay the transition from MCI to dementia.<\/jats:p>","DOI":"10.31083\/jin48660","type":"journal-article","created":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:18:12Z","timestamp":1783419492000},"source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Microbiome-Kynurenine Axis in Mild Cognitive Impairment: From Gut to Brain"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1464-0869","authenticated-orcid":true,"given":"Jiaxing","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7903-3387","authenticated-orcid":true,"given":"Haihua","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9877-3670","authenticated-orcid":true,"given":"Yingke","family":"Ouyang","sequence":"additional","affiliation":[{"name":"College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5421-5351","authenticated-orcid":true,"given":"Ting","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Preventive Center, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 410010 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2818-8511","authenticated-orcid":true,"given":"Qianyan","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8369-0021","authenticated-orcid":true,"given":"Weiai","family":"Liu","sequence":"additional","affiliation":[{"name":"Acupuncture Department, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 410010 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5803-9644","authenticated-orcid":true,"given":"Shulin","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Preventive Center, The Second Affiliated Hospital of Hunan University of Chinese Medicine, 410010 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4860-7533","authenticated-orcid":true,"given":"Mi","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Acupuncture & Tuina and Rehabilitation, Hunan University of Chinese Medicine, 410208 Changsha, Hunan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,6,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Salari N, Lotfi F, Abdolmaleki A, Heidarian P, Rasoulpoor S, Fazeli J, et al. 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