Can oral bacteria make heart disease worse?

By Dr. Liji Thomas, MDReviewed by Lauren HardakerSep 1 2025

Scientists have discovered how mouth bacteria hide inside artery walls, escaping detection until they erupt and spark the inflammation that can cause plaques to rupture.

Study: Viridans Streptococcal Biofilm Evades Immune Detection and Contributes to Inflammation and Rupture of Atherosclerotic Plaques. Image credit: Cata Arango/Shutterstock.com

Bacterial DNA from oral, respiratory, gut, and skin taxa has been reported in plaques. Its presence hints that chronic inflammation is key to atherosclerosis. A recent study published in the Journal of the American Heart Association explores the role of chronic plaque inflammation triggered by bacteria and the immune response to them in atherosclerosis.

Introduction

Atherosclerosis is a chronic subclinical inflammation caused by the oxidation of low-density lipoprotein (LDL), which is deposited within the endothelial cells of the coronary arteries to form an atheroma. This deposition, as well as its progression and eventual rupture, is driven by inflammation.

Prior research suggests that the innate immune system recognizes oxidized LDL via pattern recognition receptors like the Toll-like receptors (TLR). The primary recognition site in oxidized LDL is phosphocholine, which is also present in multiple bacteria, such as Streptococcus pneumoniae.

Immune responses to bacterial infections and to atheroma-promoting inflammatory molecules are shared. For instance, TLR2 and TLR4 receptors are important elements in the pathogen-associated molecular pattern mediating immune recognition of many bacteria. They are also found on multiple host structures, like oxidized LDL, and activate pro-inflammatory signaling pathways.

This raises the question of whether plaque formation involves infection. Nearly 50 years ago, the presence of Chlamydia and dental infections in patients with heart disease spurred the infection hypothesis. However, despite a few promising results, mostly from smaller trials, most of the antibiotic trials that took place during that period failed to show protection against recurrent cardiovascular events.

Another possibility was that biofilm-forming bacteria caused chronic inflammation that failed to activate innate immunity. The biofilm also conferred resistance to antibiotic action, perhaps explaining the lack of benefit from antibiotics. Some unknown factors may trigger the dormant biofilm, causing virulent bacteria to eat away at the protective coating and escape into the atheroma, causing infection.

The current study sought to find evidence for this hypothesis. The authors have earlier reported finding viridans streptococci in multiple vascular thrombotic sites, including those from patients with heart attacks, deep vein thrombosis, and acute ischemic stroke.

Viridans streptococci

Viridans streptococci are harmless oral cavity commensals. They initiate dental plaque formation (the oral biofilm), and are most likely to be found in the blood after dental procedures. They are also the most common microbes to be isolated in infective endocarditis, a biofilm-linked chronic bacterial infection of the heart lining.

However, they could simply be markers of inflammation. Alternatively, they might just happen to attach to the rough plaque surface as they pass through the bloodstream. In such a case, there would be immune activation, and the microbe would not be present only in atheromas.

In a healthy artery, complement factors coat bacteria, allowing macrophages to target them. Conversely, as hypoxia develops, new vessels begin to grow inside a growing atheroma. These bring bacteria from the blood directly to the atheroma. Bacteria may enter and circulate briefly in the bloodstream during dental procedures, and indeed, people who die of sudden cardiac death often have poor dental health.

About the study

The researchers examined coronary plaques from 121 individuals who suffered sudden death in the Tampere Sudden Death Study (TSDS) from Finland. Additional samples were taken from endarterectomy procedures performed on 96 patients. Real-time quantitative polymerase chain reaction (RT-qPCR) testing, immunohistochemistry, and genome-wide expression analysis were used, and the signaling pathways activated by bacteria were examined.

Study findings

Bacteria were detected in 65% of TSDS plaques and 58% of endarterectomy specimens. In both series, the most common was oral viridans streptococcus, which was present in 42% of coronary plaques and 43% of endarterectomies.

The investigators then used immunohistochemistry with anti-viridans streptococci antibodies to detect bacterial antigens in plaques, supporting a bacterial presence, rather than cross-reactivity to oxidized LDL. They found immunopositivity to viridans streptococci in 60% and 53% of the TSDS and endarterectomy samples, respectively. The scientists hypothesize that both may play a role in the early progression of the plaque.

The occurrence of viridans streptococcus was associated with severe atherosclerosis and death due to coronary heart disease.

Biofilm viridans streptococci vs virulent streptococci

Most interestingly, the viridans streptococci colonized the atheroma core and wall, forming a biofilm. This shielded them from macrophages' recognition within the plaque core, whereas dispersed streptococci at the rupture site triggered innate and adaptive immunity responses. Biofilm formation is a characteristic of most chronic infections, containing extracellular polymers that mask outer bacterial wall structures from immune cells.

At rupture sites, dispersed streptococci were detected by TLR pathways, which can drive host cytokines and matrix metalloproteinases (MMPs) that weaken the fibrous cap. Weakening and rupture of the fibrous cap are critical in atherothrombosis.

Predictive value

The more advanced or complicated the plaque, the higher the rate of immunopositivity. For instance, only 11% of artery segments with minimal atheroma formation were positive for antibodies. Still, with ruptured or thrombotic plaques, viridans streptococcal infiltration was observed in 100% of ruptured plaques in the autopsy series, and 75% in the surgical series.

“This evidence suggests that viridans streptococci are not innocent bystanders in the plaque.”

The most common signaling pathway to be activated in such cases was the TLR2 pathway. Both innate and adaptive immunity were activated at the plaque locations. Genome-wide expression analysis showed that bacterial recognition pathways were overexpressed in the endarterectomy samples.

Conclusions

The study suggests that “the change from a stable soft‐core coronary atheroma into a vulnerable rupture‐prone coronary plaque, as well as the development of a symptomatic peripheral artery plaque, may be contributed to by a chronic bacterial infection in the form of a dormant biofilm.”

This corroborates the role of inflammation in secondary cardiovascular events, as shown in the CANTOS (Canakinumab Anti‐Inflammatory Thrombosis Outcomes Study) trial. These findings may also present new diagnostic and preventive targets in atherosclerosis.

Further research could uncover the potential protective role of a short course of antibiotics during acute myocardial infarction to prevent complications due to virulent streptococcal plaque invasion.

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