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

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.