{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T21:57:56Z","timestamp":1792706276138,"version":"4.5.0"},"reference-count":126,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"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. Immunol."],"abstract":"<jats:p>Trained immunity (TI) reveals that innate immune cells acquire long-term functional memory through metabolic and epigenetic reprogramming. This review examines TI in chronic liver diseases and periodontitis, proposing the \u201cLiver-Gut-Immune-Oral Axis\u201d as a framework where TI bridges these comorbidities. The forward pathway, currently inferred from mechanistic and associative studies, proposes that liver-gut dysfunction induces bone marrow training, generating hyper-reactive monocytes that amplify periodontal inflammation. The reverse pathway, similarly conceptual, proposes that periodontal pathogens reprogram hematopoietic progenitors, accelerating liver disease progression. Both converge on shared metabolic-epigenetic reprogramming circuits. We emphasize that this axis represents a conceptual framework synthesized from current mechanistic and associative evidence; its validity as an integrated, causally-linked biological system awaits direct experimental validation. Targeting TI with metabolic modulators, epigenetic drugs, or periodontal interventions offers strategies to disrupt this cycle and advance precision medicine for inflammatory comorbidities.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1855561","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T04:38:01Z","timestamp":1780547881000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Trained immunity as a systemic bridge: the liver-gut-immune-oral axis in the comorbidity of chronic liver disease and periodontitis"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiang","family":"Li","sequence":"first","affiliation":[{"name":"Kunming Medical University","place":["Kunming, Yunnan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guodong","family":"Lv","sequence":"additional","affiliation":[{"name":"Kunming Medical University","place":["Kunming, Yunnan, 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