Gut microbiota, dysbiosis and atrial fibrillation. Arrhythmogenic mechanisms and potential clinical implications

Author:

Gawałko Monika1234ORCID,Agbaedeng Thomas A5ORCID,Saljic Arnela4ORCID,Müller Dominik N678910,Wilck Nicola678910ORCID,Schnabel Renate911ORCID,Penders John12,Rienstra Michiel13ORCID,van Gelder Isabelle13ORCID,Jespersen Thomas4ORCID,Schotten Ulrich14ORCID,Crijns Harry J G M3,Kalman Jonathan M1516ORCID,Sanders Prashanthan5ORCID,Nattel Stanley1718ORCID,Dobrev Dobromir21719,Linz Dominik34520ORCID

Affiliation:

1. 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland

2. Institute of Pharmacology, West German Heart and Vascular Centre, University Duisburg-Essen, Duisburg, Germany

3. Department of Cardiology, Maastricht University Medical Centre, Cardiovascular Research Institute Maastricht, Universiteitssingel 50, 6229 ER Maastricht, The Netherlands

4. Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

5. Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, University of Adelaide, Adelaide, Australia

6. Experimental and Clinical Research Center, Cooperation of Charité-Universitätsmedizin Berlin and Max Delbrück Centre for Molecular Medicine, Berlin, Germany

7. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany

8. Max Delbrück Centre for Molecular Medicine in the Helmholtz Association, Berlin, Germany

9. DZHK (German Centre for Cardiovascular Research), Berlin, Germany

10. Berlin Institute of Health (BIH), Berlin, Germany

11. Department of General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany

12. Department of Medical Microbiology, Care and Public Health Research Institute (CAPHRI), School for Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Centre, Maastricht, The Netherlands

13. Department of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

14. Department of Physiology, University Maastricht, Maastricht, The Netherlands

15. Department of Cardiology, Royal Melbourne Hospital, Melbourne, Australia

16. Department of Medicine, University of Melbourne, Melbourne, Australia

17. Department of Pharmacology, Medicine and Research Centre, Montréal Heart Institute, University de Montréal, McGill University, Montréal, QC, Canada

18. IHU LIRYC and Fondation Bordeaux Université, Bordeaux, France

19. Department of Molecular Physiology & Biophysics, Baylor College of Medicine, Houston, TX, USA

20. Department of Cardiology, Radboud University Medical Centre, Nijmegen, The Netherlands

Abstract

Abstract Recent preclinical and observational cohort studies have implicated imbalances in gut microbiota composition as a contributor to atrial fibrillation (AF). The gut microbiota is a complex and dynamic ecosystem containing trillions of microorganisms, which produces bioactive metabolites influencing host health and disease development. In addition to host-specific determinants, lifestyle-related factors such as diet and drugs are important determinants of the gut microbiota composition. In this review, we discuss the evidence suggesting a potential bidirectional association between AF and gut microbiota, identifying gut microbiota-derived metabolites as possible regulators of the AF substrate. We summarize the effect of gut microbiota on the development and progression of AF risk factors, including heart failure, hypertension, obesity, and coronary artery disease. We also discuss the potential anti-arrhythmic effects of pharmacological and diet-induced modifications of gut microbiota composition, which may modulate and prevent the progression to AF. Finally, we highlight important gaps in knowledge and areas requiring future investigation. Although data supporting a direct relationship between gut microbiota and AF are very limited at the present time, emerging preclinical and clinical research dealing with mechanistic interactions between gut microbiota and AF is important as it may lead to new insights into AF pathophysiology and the discovery of novel therapeutic targets for AF.

Funder

Canadian Institutes of Health Research

Heart and Stroke Foundation of Canada

National Institutes of Health

German Research Foundation

European Union (large-scale integrative project MEASTRIA

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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