{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:24:40Z","timestamp":1787163880918,"version":"build-2736575974"},"reference-count":165,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>Depression has a high global prevalence and is a common mental\u2013emotional disorder that severely jeopardizes human health. However, current treatment options remain limited, necessitating the exploration of novel pathological mechanisms and intervention targets. Recent studies indicate that periodontitis, as a prevalent chronic oral infectious disease, not only causes local microbial dysbiosis and inflammatory responses but may also influence central nervous system function through the \u201coral-gut-brain axis,\u201d thereby contributing to the pathogenesis and progression of neurodegenerative diseases such as Alzheimer\u2019s disease, Parkinson\u2019s disease, and multiple sclerosis, as well as neuropsychiatric disorders like depression. This review systematically examines the impact of periodontitis on oral microbiota and its subsequent translocation and colonization in the gut microbiota through pathways including swallowing and bloodstream circulation, ultimately leading to structural and functional dysregulation of the gut microbiota. The interaction between oral and gut microbiota can influence the brain through the \u201cgut-brain axis,\u201d including disturbances in neurotransmitter metabolism, activation of systemic immune responses, and direct or indirect effects of bacterial metabolites (such as short-chain fatty acids, lipopolysaccharides, etc.) on the blood\u2013brain barrier and neural function. This suggests that periodontal health management may serve as a novel strategy for the prevention and treatment of depression. This article further summarizes the potential of oral interventions for periodontitis (such as mechanical debridement and local\/systemic antimicrobial therapy), microbiota modulation methods (such as probiotics, prebiotics, and fecal microbiota transplantation), and multidisciplinary collaborative comprehensive treatment strategies in improving microbial homeostasis and alleviating depressive symptoms. Finally, this paper points out the current research limitations in mechanistic details, causal relationships, and clinical translation, while envisioning the feasibility and prospects of developing personalized treatment strategies by targeting the \u201coral-gut-brain axis\u201d in the future.<\/jats:p>","DOI":"10.3389\/fmicb.2026.1778744","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T06:00:25Z","timestamp":1775800825000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["The oral-gut-brain axis: how periodontitis influence depression"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhixuan","family":"Li","sequence":"first","affiliation":[{"name":"Liaoning Provincial Key Laboratory of Oral Disease, Department of Periodontics, School and Hospital of Stomatology, China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengzhi","family":"Xie","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital of Dalian Medical University","place":["Dalian, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunling","family":"Pan","sequence":"additional","affiliation":[{"name":"Liaoning Provincial Key Laboratory of Oral Disease, Department of Periodontics, School and Hospital of Stomatology, China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"814","DOI":"10.3390\/microorganisms13040814","article-title":"The oral-gut microbiome-brain axis in cognition","volume":"13","author":"Adil","year":"2025","journal-title":"Microorganisms"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.1016\/j.cell.2021.03.022","article-title":"SnapShot: the microbiota-gut-brain axis","volume":"184","author":"Agirman","year":"2021","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1111\/jre.13406","article-title":"Geographic influence on subgingival microbiota in health and periodontitis: a multinational shotgun metagenomic study","volume":"60","author":"Alexandre","year":"2025","journal-title":"J. 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