Gut microbiome and atrial fibrillation-results from a large population-based study

Joonatan Palmu; Christin S. Boerschel; Alfredo Ortega-Alonso; Lajos Marko; 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

doi:10.1016/j.ebiom.2023.104583

Gut microbiome and atrial fibrillation-results from a large population-based study

Joonatan Palmu, Christin S. Boerschel, Alfredo Ortega-Alonso, Lajos Marko, 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^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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 treat-ment 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. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Original language	English
Article number	104583
Number of pages	11
Journal	EBioMedicine
Volume	91
Issue number	1
Early online date	1 Apr 2023
DOIs	https://doi.org/10.1016/j.ebiom.2023.104583
Publication status	Published - 1 May 2023

Keywords

Atrial fibrillation
Gut microbiome
Metagenomics
Epidemiology
TRIMETHYLAMINE-N-OXIDE
BLOOD-PRESSURE
HEART-FAILURE
RISK

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10.1016/j.ebiom.2023.104583Licence: CC BY-NC-ND

Cite this

Palmu, J., Boerschel, C. S., Ortega-Alonso, A., Marko, L., Inouye, M., Jousilahti, P., Salido, R. A., Sanders, K., Brennan, C., Humphrey, G. C., Sanders, J. G., Gutmann, F., Linz, D., Salomaa, V., Havulinna, A. S., Forslund, S. K., Knight, R., Lahti, L., Niiranen, T., & Schnabel, R. B. (2023). Gut microbiome and atrial fibrillation-results from a large population-based study. EBioMedicine, 91(1), Article 104583. https://doi.org/10.1016/j.ebiom.2023.104583

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title = "Gut microbiome and atrial fibrillation-results from a large population-based study",

abstract = "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 treat-ment 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. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).",

keywords = "Atrial fibrillation, Gut microbiome, Metagenomics, Epidemiology, TRIMETHYLAMINE-N-OXIDE, BLOOD-PRESSURE, HEART-FAILURE, RISK",

author = "Joonatan Palmu and Boerschel, {Christin S.} and Alfredo Ortega-Alonso and Lajos Marko and Michael Inouye and Pekka Jousilahti and Salido, {Rodolfo A.} and Karenina Sanders and Caitriona Brennan and Humphrey, {Gregory C.} and Sanders, {Jon G.} and Friederike Gutmann and Dominik Linz and Veikko Salomaa and Havulinna, {Aki S.} and Forslund, {Sofia K.} and Rob Knight and Leo Lahti and Teemu Niiranen and Schnabel, {Renate B.}",

year = "2023",

month = may,

day = "1",

doi = "10.1016/j.ebiom.2023.104583",

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volume = "91",

journal = "EBioMedicine",

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Palmu, J, Boerschel, CS, Ortega-Alonso, A, Marko, L, Inouye, M, Jousilahti, P, Salido, RA, Sanders, K, Brennan, C, Humphrey, GC, Sanders, JG, Gutmann, F, Linz, D, Salomaa, V, Havulinna, AS, Forslund, SK, Knight, R, Lahti, L, Niiranen, T & Schnabel, RB 2023, 'Gut microbiome and atrial fibrillation-results from a large population-based study', EBioMedicine, vol. 91, no. 1, 104583. https://doi.org/10.1016/j.ebiom.2023.104583

TY - JOUR

T1 - Gut microbiome and atrial fibrillation-results from a large population-based study

AU - Palmu, Joonatan

AU - Boerschel, Christin S.

AU - Ortega-Alonso, Alfredo

AU - Marko, Lajos

AU - Inouye, Michael

AU - Jousilahti, Pekka

AU - Salido, Rodolfo A.

AU - Sanders, Karenina

AU - Brennan, Caitriona

AU - Humphrey, Gregory C.

AU - Sanders, Jon G.

AU - Gutmann, Friederike

AU - Linz, Dominik

AU - Salomaa, Veikko

AU - Havulinna, Aki S.

AU - Forslund, Sofia K.

AU - Knight, Rob

AU - Lahti, Leo

AU - Niiranen, Teemu

AU - Schnabel, Renate B.

PY - 2023/5/1

Y1 - 2023/5/1

N2 - 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 treat-ment 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. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

AB - 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 treat-ment 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. Copyright (c) 2023 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

KW - Atrial fibrillation

KW - Gut microbiome

KW - Metagenomics

KW - Epidemiology

KW - TRIMETHYLAMINE-N-OXIDE

KW - BLOOD-PRESSURE

KW - HEART-FAILURE

KW - RISK

U2 - 10.1016/j.ebiom.2023.104583

DO - 10.1016/j.ebiom.2023.104583

M3 - Article

C2 - 37119735

SN - 2352-3964

VL - 91

JO - EBioMedicine

JF - EBioMedicine

IS - 1

M1 - 104583

ER -