In a groundbreaking study that deepens our understanding of the intricate relationship between oral health and cardiovascular disease, researchers at Hiroshima University have uncovered compelling evidence pinpointing the gum disease-causing bacterium Porphyromonas gingivalis as a direct contributor to atrial fibrosis and atrial fibrillation (AFib). This discovery, published in the esteemed journal Circulation, elucidates a microbial mechanism through which periodontal infection translocates from the oral cavity to the heart, unraveling a potential causative link between chronic periodontitis and cardiac arrhythmias.
The prevalence of AFib, a heart rhythm disorder characterized by irregular and often rapid atrial contractions, has been escalating worldwide, nearly doubling from approximately 33.5 million cases in 2010 to 60 million by 2019. This surge has motivated intensive research into underlying risk factors, including systemic inflammation typically associated with chronic infections. Among these, periodontitis—a bacterial gum disease long suspected of exacerbating cardiovascular conditions—has gained particular attention. Epidemiological data previously hinted at a 30% higher risk of AFib among individuals with periodontitis, yet the precise biological pathways remained obscure.
While systemic inflammation induced by periodontal infection was hypothesized as a principal driver facilitating vascular and cardiac disease, recent investigations revealed the presence of microbial DNA fragments not just in the bloodstream but embedded within cardiac muscle tissue, valves, and atherosclerotic plaques. Porphyromonas gingivalis, an anaerobic, Gram-negative pathogen notorious for its role in aggressive periodontitis, emerged as a prime suspect. Prior detection of this bacterium in diverse tissues such as the brain, liver, and placenta underscored its invasive capabilities, but how it expanded its reach into cardiac tissues was unknown until now.
Employing a meticulously designed animal model, the researchers introduced the highly virulent W83 strain of P. gingivalis directly into the tooth pulp of 13-week-old male mice. This model replicated key aspects of human periodontitis, enabling researchers to trace the bacterium’s systemic migration and subsequent cardiac effects over extended periods. Intracardiac electrophysiological assessments revealed no substantial change in arrhythmic susceptibility at 12 weeks post-infection. However, by 18 weeks, P. gingivalis-infected mice demonstrated a remarkable six-fold increase in AFib inducibility compared to uninfected controls, with incidence rates rising to 30% from a baseline of 5%.
Detailed histological examination uncovered significant fibrosis localized within the left atrium, a hallmark structural alteration implicated in disrupted electrical conduction and AFib development. Molecular detection techniques, including loop-mediated isothermal amplification targeting P. gingivalis-specific genetic sequences, confirmed the presence of the bacterium in cardiac tissue. Notably, this colonization was absent in control mice, corroborating the translocation hypothesis. The extent of myocardial scarring in infected mice at 18 weeks reached 21.9%, notably surpassing the 16.3% fibrosis observed in age-matched controls, suggesting that chronic P. gingivalis exposure accelerates atrial remodeling well beyond physiological aging.
Extending these findings to human subjects, the investigation analyzed left atrial tissue harvested from 68 patients undergoing cardiac surgery for AFib treatment. Consistent with animal data, P. gingivalis DNA was identified in these human cardiac samples, with bacterial load correlating positively with the clinical severity of periodontitis, thus establishing a critical association between oral infection burden and cardiac pathology.
Central to P. gingivalis’s pathogenic success is its adeptness at evading host immune defenses. The bacterium’s ability to invade host cells and circumvent autophagy-mediated degradation positions it as a "master of stealth," enabling persistent infection and subclinical inflammation. Infected mice exhibited elevated levels of galectin-3, a profibrotic biomarker implicated in extracellular matrix deposition and tissue stiffening, alongside upregulated expression of Tgfb1, a gene closely linked to cytokine-mediated fibrosis and inflammatory cascades. These molecular alterations provide mechanistic insights into how P. gingivalis infection instigates pathological atrial fibrosis.
The implications of this research are profound for both dental and cardiovascular medicine. The study underscores the importance of oral hygiene measures, such as regular tooth brushing and flossing, which may extend protective effects beyond the oral cavity to the heart by impeding bacterial entry into the bloodstream. Furthermore, periodontal treatment protocols could emerge as valuable adjunctive strategies in AFib prevention and management, particularly in patients with coexisting gum disease.
Shunsuke Miyauchi, assistant professor at Hiroshima University’s Graduate School of Biomedical and Health Sciences and lead author of the study, emphasizes the need for collaborative approaches. "Periodontal bacteria like P. gingivalis translocate into the circulatory system via periodontal lesions, eventually colonizing the left atrium where they exacerbate fibrosis and increase AFib inducibility," Miyauchi explains. "Blocking this bacterial gateway through targeted periodontal therapies may play a pivotal role in mitigating atrial fibrillation risk."
Building on these insights, ongoing research at Hiroshima University aims to dissect the cellular and molecular mechanisms by which P. gingivalis impacts atrial cardiomyocytes, the heart muscle cells responsible for electrical propagation and contraction. Elucidating these pathways will refine our understanding of microbial contributions to cardiac pathology and potentially unveil novel therapeutic targets.
This study also marks the inception of an ambitious interdisciplinary initiative in Hiroshima Prefecture, seeking to integrate medical and dental healthcare frameworks. By fostering synergy between cardiologists and dental professionals, this approach aspires to enhance prevention, diagnosis, and treatment of cardiovascular diseases influenced by oral pathogens. If successful, the model could be adopted nationwide, catalyzing a paradigm shift in comprehensive patient care.
As the scientific and clinical communities continue to unravel the enigmatic links between oral bacteria and systemic diseases, the role of pathogens like Porphyromonas gingivalis is increasingly recognized as a critical factor influencing cardiac health. This pioneering study not only substantiates that connection but also paves the way for transformative strategies combating atrial fibrillation through meticulous oral health management.
Subject of Research: The translocation of Porphyromonas gingivalis from periodontal lesions to the heart and its role in exacerbating atrial fibrosis and atrial fibrillation.
Article Title: Atrial Translocation of Porphyromonas gingivalis Exacerbates Atrial Fibrosis and Atrial Fibrillation
News Publication Date: 18-Mar-2025
Web References:
- https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.124.071310
- https://onlinelibrary.wiley.com/doi/10.1002/joa3.12921
- https://www.sciencedirect.com/science/article/pii/S0735109720377755?via%3Dihub
References: See article DOI for full publication details.
Image Credits: Courtesy of Shunsuke Miyauchi/Hiroshima University
Keywords: Health and medicine; Health care; Human health; Cardiology; Fibrillation; Cardiovascular disorders; Human heart
