Periodontal Dysbiosis and Premature Atherosclerosis: A Critical Appraisal of the Oral-Gut-Vascular Axis.

Abstract

Background/Objectives: Premature coronary artery disease (PCAD) is not fully explained by conventional risk factors, particularly in younger adults with residual inflammatory risk. This review evaluates the oral-gut-vascular axis as a mechanistic framework linking periodontal dysbiosis to premature atherosclerosis. Methods: A structured narrative search of PubMed/MEDLINE, Scopus, Embase, and Web of Science was conducted for English-language publications issued between January 2015 and June 2026. Human observational and interventional studies, mechanistic studies, systematic reviews, meta-analyses, and major scientific statements addressing periodontal disease, gut dysbiosis, barrier dysfunction, microbial metabolites, and vascular outcomes were considered. Results: Current evidence supports the biological plausibility of interconnected pathways involving periodontal pathobionts, microbial translocation, intestinal dysbiosis, increased epithelial permeability, endotoxemia, TLR2/TLR4 signaling, TMAO metabolism, oxidative stress, immune dysregulation, endothelial dysfunction, and plaque development. Candidate translational markers include hsCRP, IL-6, LPS, LBP, TMAO, oxidized LDL, adhesion molecules, salivary microbial signatures, and vascular imaging indices. Periodontal treatment and microbiome-directed strategies may reduce inflammatory burden, although effects on major cardiovascular outcomes remain unproven. Conclusions: The oral-gut-vascular axis is biologically plausible but not yet causally established in humans, and its specific relevance to PCAD remains largely inferential. Prospective PCAD-specific cohorts, standardized multi-omics, validated biomarkers, vascular imaging, and externally validated artificial-intelligence models are required to establish clinical utility and inform integrated cardio-dental prevention in younger populations.