The microbiome and rheumatic heart disease: current knowledge and future perspectives

Abstract

Rheumatic heart disease (RHD) is a cardiovascular disease caused by an autoimmune response to group A Streptococcus (GAS) infection resulting in the damage of heart valves. RHD is the most commonly acquired heart disease among children and young adults with a global burden of over 40 million cases accounting for 306,000 deaths annually. Inflammation in the heart valves caused due to molecular mimicry between the GAS antigens and host cardiac proteins is facilitated by cytokines, cross-reactive antibodies and CD4⁺ T cells. The complex interaction between genetic and environmental factors linked with erratic events leads to the loss of immunological tolerance and autoimmunity in RHD. Despite extensive research on the etiopathogenesis of RHD, the precise mechanism underpinning the initiation of acute rheumatic fever (ARF) to the progression of RHD still remains elusive. Mounting evidences support the contribution of the human microbiome in the development of several immune-mediated diseases including rheumatoid arthritis, juvenile idiopathic arthritis, Kawasaki disease, inflammatory bowel disease and type 1 diabetes. The microbiome and their metabolites could play a crucial role in the integrity of the epithelial barrier, development of the immune system, inflammation and differentiation of T cell subsets. Consequently, microbiome dysbiosis might result in autoimmunity by molecular mimicry, epitope spreading and bystander activation. This review discusses various aspects of the interaction between the microbiome and the immune system in order to reveal causative links relating dysbiosis and autoimmune diseases with special emphasis on RHD.

Keywords:

• Rheumatic fever
• rheumatic heart disease
• microbiome
• autoimmunity
• cardiovascular disease

Acknowledgments

We acknowledge the Department of Health Research, Government of India, for the support of this work under the scheme: Multi-Disciplinary Research Unit, Madurai Medical College, Madurai, Tamil Nadu, India.

Authors contributions

All authors met the International Committee of Medical Journal Editors (ICMJE) criteria for authorship, contributed to the intellectual content of the study, and approved the final version of the article.

Ethics statement

All analyses of the present work were depended on previously published literatures and public databases, there were no human participants included in our study. Thus, this work does not need any ethical approval and patient consent.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This work was supported by the Department of Health Research, Ministry of Health and Family Welfare, Government of India under grant number [No. V25011/464/2015/HR].