{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:02:53Z","timestamp":1789390973035,"version":"build-2803163510"},"reference-count":175,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:00:00Z","timestamp":1789171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Depression and Alzheimer\u2019s disease are among the most prevalent and disabling disorders worldwide, imposing a substantial social, economic, and healthcare burden. Increasing evidence suggests that these conditions share several pathophysiological mechanisms, including chronic inflammation, oxidative stress, mitochondrial dysfunction, altered neurotransmission, and gut microbiota dysbiosis. In recent years, the microbiota\u2013gut\u2013brain axis has emerged as a key regulatory system linking gastrointestinal, immune, metabolic, and neural functions. Within this complex network, the tryptophan\u2013kynurenine pathway has gained considerable attention as a critical mediator connecting gut microbial activity, immune responses, and central nervous system function. This review examines the role of the microbiota\u2013gut\u2013brain axis and the tryptophan\u2013kynurenine pathway in the development and progression of depression and Alzheimer\u2019s disease. Particular emphasis is placed on the regulation of tryptophan metabolism by gut microbiota, the inflammatory activation of indoleamine 2,3-dioxygenase, and the generation of neuroactive kynurenine metabolites. Dysregulation of these processes may reduce serotonin synthesis while promoting the accumulation of neurotoxic compounds such as quinolinic acid and 3-hydroxykynurenine, thereby contributing to neuroinflammation, excitotoxicity, cognitive decline, and depressive symptoms. Current evidence also highlights the therapeutic potential of interventions targeting gut microbiota composition and kynurenine pathway activity. A better understanding of these interconnected mechanisms may facilitate the identification of novel biomarkers and the development of personalized strategies for the prevention and treatment of both psychiatric and neurodegenerative disorders.<\/jats:p>","DOI":"10.3390\/ijms27188122","type":"journal-article","created":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:09:51Z","timestamp":1789387791000},"page":"8122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Tryptophan\u2013Kynurenine Pathway as a Key Mediator of the Gut\u2013Brain Axis in Depression and Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4738-5775","authenticated-orcid":false,"given":"Lucia Maria","family":"Procopciuc","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0944-3161","authenticated-orcid":false,"given":"Adriana Corina","family":"Hangan","sequence":"additional","affiliation":[{"name":"Department of Inorganic Chemistry, Faculty of Pharmacy, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sidonia","family":"Gog-Bogdan","sequence":"additional","affiliation":[{"name":"Department of Sugery and ATI, Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine, 400372 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4920-4760","authenticated-orcid":false,"given":"Roxana Liana","family":"Lucaciu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry and Clinical Laboratory, Faculty of Pharmacy, \u201cIuliu-Ha\u021bieganu\u201d University of Medicine and Pharmacy, 400349 Cluj-Napoca, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"ref_1","unstructured":"Institute for Health Metrics and Evaluation (2024). 2021 Global Burden of Disease (GBD) [Online Database], Institute for Health Metrics and Evaluation. 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