PORPHYROMONAS GINGIVALIS AND THE BRAIN-HEART AXIS: REASSESSING CAUSALITY IN ATHEROSCLEROSIS AND STROKE

Abstract

Periodontitis is among the most prevalent chronic inflammatory conditions worldwide, and Porphyromonas gingivalis is its most extensively characterised keystone pathogen. An influential literature proposes that this organism links oral dysbiosis to atherosclerosis and ischaemic stroke, forming a putative brain-heart axis. The mechanistic case is detailed: P. gingivalis, its gingipains and its outer membrane vesicles invade endothelial cells, suppress endothelial nitric oxide synthase, drive Drp1-dependent mitochondrial fission, promote scavenger-receptor-mediated foam cell formation, oxidise high-density lipoprotein, distort T-helper 17 and regulatory T-cell balance, and increase blood-brain barrier permeability through Mfsd2a and caveolin-1 dependent transcytosis. Animal models show accelerated atheroma in infected hyperlipidaemic mice, and observational studies report elevated stroke risk in periodontitis, with pooled relative risks generally between 1.2 and 1.9. Three lines of human evidence resist a causal reading. First, detection of P. gingivalis in vascular and cerebral tissue is markedly inconsistent, with prevalence ranging from zero to 79% and cerebral thrombus studies identifying viridans streptococci rather than P. gingivalis. Second, randomised periodontal treatment trials improve surrogate endpoints such as flow-mediated dilatation and blood pressure without reducing stroke or myocardial infarction. Third, Mendelian randomisation using genetic proxies for periodontitis shows null effects on ischaemic stroke, coronary artery disease and carotid intima-media thickness. This review synthesises epidemiological, microbiological, mechanistic, interventional and genetic evidence, appraises it against the Bradford Hill viewpoints, and argues that P. gingivalis is better regarded as a modifier of established vascular injury than as a proven independent cause.