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

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Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Palmu J, Börschel CS, Ortega-Alonso A, Markó 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
Journal
EBioMedicine
Year
2023
Keywords:
Atrial fibrillation, Epidemiology, Gut microbiome, Metagenomics
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.

Experiment 1


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/15

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Chinelsy, ChiomaBlessing

Subjects

Location of subjects
Finland
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Atrial fibrillation A-fib,AF,AF - Atrial fibrillation,AFib,atrial fibrillation,atrial fibrillation (disease),Atrial fibrillation (disorder),Atrial Fibrillations,Auricular Fibrillation,Auricular Fibrillations,Fibrillation, Atrial,Fibrillation, Auricular,Fibrillations, Atrial,Fibrillations, Auricular,Atrial fibrillation
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Individuals without Prevalent Atrial Fibrillation (AF)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Individuals with Prevalent Atrial Fibrillation (AF)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants with prevalent atrial fibrillation. Atrial fibrillation (AF) is an important heart rhythm disorder in aging populations
Group 0 sample size Number of subjects in the control (unexposed) group
6647
Group 1 sample size Number of subjects in the case (exposed) group
116
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
None.

Lab analysis

Sequencing type
WMS
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, diabetes mellitus, physical activity, sex, smoking status, blood pressure, alcohol consumption measurement, Confounders controlled for: "heart failure" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.heart failure, Confounders controlled for: "antihypertensive medication use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.antihypertensive medication use, total cholesterol measurement

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/15

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Source: Figure 2, Table 2

Description: Abundant genera in individuals with Prevalent Atrial Fibrillation (AF) compared to individuals without Prevalent AF

Abundance in Group 1: increased abundance in Individuals with Prevalent Atrial Fibrillation (AF)

NCBI Quality ControlLinks
Eisenbergiella
Enorma
Enterobacter
Kluyvera

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/15

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Source: Figure 2, Table 2

Description: Abundant genera in individuals with Prevalent Atrial Fibrillation (AF) compared to individuals without Prevalent AF

Abundance in Group 1: decreased abundance in Individuals with Prevalent Atrial Fibrillation (AF)

NCBI Quality ControlLinks
Bacteroides
Bifidobacterium
Holdemanella
Parabacteroides
Turicibacter

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Experiment 2


Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/16

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Tolulopeo, Chinelsy, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Individuals without Incident Atrial Fibrillation (AF)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Individuals with Incident Atrial Fibrillation (AF)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Incident AF refers to new cases of atrial fibrillation that occurred during the follow-up period of the study, among individuals who did not have a history of atrial fibrillation at baseline.
Group 1 sample size Number of subjects in the case (exposed) group
539

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, body mass index, blood pressure, smoking status, alcohol consumption measurement, diabetes mellitus, Confounders controlled for: "heart failure" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.heart failure, Confounders controlled for: "antihypertensive medication use" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.antihypertensive medication use, total cholesterol measurement

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/17

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Source: Figure 2, Table 3

Description: Abundant genera in individuals with Incident Atrial Fibrillation (AF) compared to individuals without Incident AF

Abundance in Group 1: increased abundance in Individuals with Incident Atrial Fibrillation (AF)

NCBI Quality ControlLinks
Bifidobacterium
Enorma
Lactococcus
Mitsuokella
Sellimonas

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Signature 2

Reviewed Marked as Reviewed by ChiomaBlessing on 2024-2-13

Curated date: 2023/10/17

Curator: Iram jamshed

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing

Source: Figure 2, Table 3

Description: Abundant genera in individuals with Incident Atrial Fibrillation (AF) compared to individuals without Incident AF

Abundance in Group 1: decreased abundance in Individuals with Incident Atrial Fibrillation (AF)

NCBI Quality ControlLinks
Hungatella
Tyzzerella
Sanguibacteroides

Revision editor(s): Iram jamshed, Tolulopeo, ChiomaBlessing