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  • Review Article
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The oral microbiome in the pathophysiology of cardiovascular disease

Nature Reviews Cardiology volume 20, pages 386–403 (2023)Cite this article

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Abstract

Despite advances in our understanding of the pathophysiology of many cardiovascular diseases (CVDs) and expansion of available therapies, the global burden of CVD-associated morbidity and mortality remains unacceptably high. Important gaps remain in our understanding of the mechanisms of CVD and determinants of disease progression. In the past decade, much research has been conducted on the human microbiome and its potential role in modulating CVD. With the advent of high-throughput technologies and multiomics analyses, the complex and dynamic relationship between the microbiota, their ‘theatre of activity’ and the host is gradually being elucidated. The relationship between the gut microbiome and CVD is well established. Much less is known about the role of disruption (dysbiosis) of the oral microbiome; however, interest in the field is growing, as is the body of literature from basic science and animal and human investigations. In this Review, we examine the link between the oral microbiome and CVD, specifically coronary artery disease, stroke, peripheral artery disease, heart failure, infective endocarditis and rheumatic heart disease. We discuss the various mechanisms by which oral dysbiosis contributes to CVD pathogenesis and potential strategies for prevention and treatment.

Key points

  • The incidence and prevalence of cardiovascular diseases (CVDs) are increasing despite advances in our understanding of their pathophysiology and an expanded arsenal of treatment options.

  • An association between the oral microbiome (or oralome) and cardiovascular inflammation and CVD is supported by a growing body of epidemiological studies, systematic reviews and basic science investigations.

  • Validated links exist between oral dysbiosis and CVDs, including atherosclerotic diseases, heart failure, infective endocarditis and rheumatic heart disease.

  • The mechanisms by which oral dysbiosis contributes to CVD include immunomodulation; endothelial dysfunction; molecular mimicry and antibody cross-reactivity; protein citrullination; platelet activation, aggregation and thrombogenesis; arterial invasion; and systemic inflammation.

  • Targeting oral dysbiosis in a clinical setting could be an important component of CVD management.

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Fig. 1: Development and progression of atherosclerotic cardiovascular disease.
Fig. 2: Oral dysbiosis in the pathogenesis of atherosclerotic cardiovascular disease.
Fig. 3: Oral dysbiosis in the pathogenesis of heart failure.
Fig. 4: Oral dysbiosis in the pathogenesis of infective endocarditis.
Fig. 5: Oral dysbiosis in the pathogenesis of RHD.

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Acknowledgements

A.T. acknowledges funding from the Skye Foundation, the Life Healthcare Group and The Mandela Rhodes Foundation. E.N.L. acknowledges funding from the National Research Foundation of South Africa and the Carnegie Corporation of New York. N.A.B.N. acknowledges funding from the National Research Foundation, South African Medical Research Council, Medical Research Council United Kingdom, and the Lily and Ernst Hausmann Trust. The funders had no role in the design and conduct of the research.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Andrea Tonelli & Ntobeko A. B. Ntusi

  2. Cardiovascular Research Unit, Christiaan Barnard Division of Cardiothoracic Surgery, Department of Surgery, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Andrea Tonelli

  3. Cape Heart Institute, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Andrea Tonelli, Evelyn N. Lumngwena & Ntobeko A. B. Ntusi

  4. Extramural Research Unit on the Intersection of Noncommunicable Diseases and Infectious Disease, South African Medical Research Council, Cape Town, South Africa

    Andrea Tonelli & Ntobeko A. B. Ntusi

  5. School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa

    Evelyn N. Lumngwena

  6. Centre for the Study of Emerging and Re-emerging Infections, Institute for Medical Research and Medicinal Plant Studies, Ministry of Scientific Research and Innovation, Yaoundé, Cameroon

    Evelyn N. Lumngwena

  7. Cape Universities Body Imaging Centre, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Ntobeko A. B. Ntusi

  8. Wellcome Centre for Infectious Disease Research, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa

    Ntobeko A. B. Ntusi

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Contributions

E.N.L. and N.A.B.N. conceived the microbiome project. A.T., E.N.L. and N.A.B.N. researched data for the article, and A.T. compiled the figures. All the authors contributed to discussion of content, writing of the manuscript and reviewing/editing the article before submission.

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Correspondence to Ntobeko A. B. Ntusi.

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Glossary

Dysbiosis

Any change to the composition or function, in terms of abundance and diversity, of resident commensal microbes relative to the composition or role in healthy individuals. Owing to the close, bidirectional orchestration of these communities and human physiology, perturbations in abundance and diversity can lead to inflammatory and metabolic abnormalities that contribute to a plethora of diseases.

Endotoxaemia

Translocation of lipopolysaccharide in the circulation, which can arise from infections or commensal bacteria. The oral cavity is an important source of endotoxaemia. The mouth harbours approximately 100–200 commensal bacterial species and has higher phylogenetic diversity than any other location in the body.

Eubiosis

A healthy or optimal microbiome, one with diversity and uniformity of respective microbiota, at abundances characteristically found in healthy individuals. A eubiotic microbiome confers a protective and beneficial physiological effect, helping to maintain the optimal homeostatic balance while ensuring appropriate training and maintenance of the immunological system.

Microbiome

A characteristic community of microbiota, including bacteria, archaea, fungi, viruses, protists and algae, occupying a specific habitat, including their ‘theatre of activity’, consisting of various microbial structural elements (proteins, lipids and polysaccharides and nucleic acids), internal and external structural elements (including microbial metabolites and mobile genetic elements) and the immediate environmental conditions. Together, these elements form unique ecological niches that are dynamic and adaptable through time, integrating with host physiology to influence function and health.

Multiomics

A comprehensive, or global, assessment of a set of molecules. The term is commonly applied to high-throughput technologies in the fields of genomics, proteomics, transcriptomics, metabolomics and lipidomics. When these fields are combined, specifically looking at data from a ‘multiomics’ perspective, the flow of information that underlies disease, from gene to phenotype, can be elucidated.

Oralome

The overarching term using to summarize the dynamic interactions between the ecological community of oral microorganisms, including bacteria, fungi, viruses, archaea and protozoa that live within the oral cavity of the host.

Periodontitis

A chronic inflammatory disease associated with destruction of connective tissue of gingiva, periodontal ligament and alveolar bone following untreated or improperly treated gingivitis. Bacterial biofilms (dental plaque), predominantly composed of the viridans group streptococci, are the primary aetiological factors for the inflammatory process of gingivitis, leading to subsequent destruction of periodontal tissues.

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Tonelli, A., Lumngwena, E.N. & Ntusi, N.A.B. The oral microbiome in the pathophysiology of cardiovascular disease. Nat Rev Cardiol 20, 386–403 (2023). https://doi.org/10.1038/s41569-022-00825-3

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