Gut microbiome and atrial fibrillation—results from a large population-based studyResearch in context
Joonatan Palmu,
Christin S. Börschel,
Alfredo Ortega-Alonso,
Lajos Markó,
Michael Inouye,
Pekka Jousilahti,
Rodolfo A. Salido,
Karenina Sanders,
Caitriona Brennan,
Gregory C. Humphrey,
Jon G. Sanders,
Friederike Gutmann,
Dominik Linz,
Veikko Salomaa,
Aki S. Havulinna,
Sofia K. Forslund,
Rob Knight,
Leo Lahti,
Teemu Niiranen,
Renate B. Schnabel
Affiliations
Joonatan Palmu
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Finland
Christin S. Börschel
Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany
Alfredo Ortega-Alonso
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Neuroscience Center, University of Helsinki, Helsinki, Finland; Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland
Lajos Markó
Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité – Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
Michael Inouye
Cambridge Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia; Cambridge Baker Systems Genomics Initiative, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
Pekka Jousilahti
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland
Rodolfo A. Salido
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
Karenina Sanders
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
Caitriona Brennan
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
Gregory C. Humphrey
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA
Jon G. Sanders
Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA; Cornell Institute for Host-Microbe Interaction and Disease, Cornell University, Ithaca, NY, USA
Friederike Gutmann
Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité – Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany
Dominik Linz
Department of Cardiology, Maastricht University Medical Centre and Cardiovascular Research Institute Maastricht, Maastricht, the Netherlands; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Centre for Heart Rhythm Disorders, Royal Adelaide Hospital, and University of Adelaide, Adelaide, Australia; Department of Cardiology, Radboud University Medical Centre, Nijmegen, the Netherlands
Veikko Salomaa
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland
Aki S. Havulinna
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Institute for Molecular Medicine Finland, FIMM - HiLIFE, Helsinki, Finland
Sofia K. Forslund
Experimental and Clinical Research Center, a Cooperation of Charité-Universitätsmedizin and the Max-Delbrück Center, Berlin, Germany; Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany; Charité – Universitätsmedizin Berlin, Berlin, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Germany; Structural and Computational Biology, European Molecular Biology Laboratory, Heidelberg, Germany
Rob Knight
Center for Microbiome Innovation, Jacobs School of Engineering, University of California San Diego, La Jolla, CA, USA; Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA, USA; Department of Computer Science & Engineering, University of California San Diego, La Jolla, CA, USA
Leo Lahti
Department of Computing, University of Turku, Turku, Finland
Teemu Niiranen
Department of Public Health and Welfare, Finnish Institute for Health and Welfare, Helsinki, Turku, Finland; Department of Internal Medicine, Turku University Hospital and University of Turku, Finland
Renate B. Schnabel
Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Hamburg, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, Hamburg, Germany; Corresponding author. Department of Cardiology, University Heart and Vascular Centre Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Summary: Background: Atrial fibrillation (AF) is an important heart rhythm disorder in aging populations. The gut microbiome composition has been previously related to cardiovascular disease risk factors. Whether the gut microbial profile is also associated with the risk of AF remains unknown. Methods: We examined the associations of prevalent and incident AF with gut microbiota in the FINRISK 2002 study, a random population sample of 6763 individuals. We replicated our findings in an independent case–control cohort of 138 individuals in Hamburg, Germany. Findings: Multivariable-adjusted regression models revealed that prevalent AF (N = 116) was associated with nine microbial genera. Incident AF (N = 539) over a median follow-up of 15 years was associated with eight microbial genera with false discovery rate (FDR)-corrected P < 0.05. Both prevalent and incident AF were associated with the genera Enorma and Bifidobacterium (FDR-corrected P < 0.001). AF was not significantly associated with bacterial diversity measures. Seventy-five percent of top genera (Enorma, Paraprevotella, Odoribacter, Collinsella, Barnesiella, Alistipes) in Cox regression analyses showed a consistent direction of shifted abundance in an independent AF case–control cohort that was used for replication. Interpretation: Our findings establish the basis for the use of microbiome profiles in AF risk prediction. However, extensive research is still warranted before microbiome sequencing can be used for prevention and targeted treatment of AF. Funding: This study was funded by European Research Council, German Ministry of Research and Education, Academy of Finland, Finnish Medical Foundation, and the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, and the Paavo Nurmi Foundation.
