{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T01:55:28Z","timestamp":1772675728030,"version":"3.50.1"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"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. Dent. Med."],"abstract":"<jats:p>Periodontal disease is a recognized risk factor for sepsis, infective endocarditis, and cardiovascular disease. Oral bacteria, including viridans group of Streptococci, abundant in healthy oral microbiota, are frequently implicated in bacteremia and chronic inflammation, both contributing factors to systemic diseases. Yet the immunological mechanisms linking oral and systemic disease remain incompletely defined. This article proposes that \u201coral tolerance\u201d\u2014the immune system's suppression of responses to antigens repeatedly encountered via the oral route\u2014may heighten susceptibility to systemic diseases, by impairing early systemic innate immune engagement with oral bacteria entering the bloodstream. Specifically, tolerogenic-signaling by gut-associated lymphoid tissue may condition circulating innate immune cells toward a regulatory phenotype, delaying effective pathogen clearance and promoting cytokine disorientation. This brief review outlines mechanistic insights, explores microbial influences, and suggests experimental approaches, aiming to advance research in oral-systemic health.<\/jats:p>","DOI":"10.3389\/fdmed.2025.1700937","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T06:27:41Z","timestamp":1765866461000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Oral tolerance, a potential driver of systemic disease risk in periodontal patients"],"prefix":"10.3389","volume":"6","author":[{"given":"Alan E.","family":"Hubbs","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"B1","first-page":"21","article-title":"Association of the oral flora with important medical diseases","volume":"4","author":"Loesche","year":"1997","journal-title":"Curr Opin 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