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Gut Microbiome and Metabolite Alterations in Atrial Fibrillation
40 Pages Posted: 5 Dec 2024
More...Abstract
Background: Classical cardiovascular risk factors (CVRF) cannot fully explain the pathogenesis of atrial fibrillation (AF). Recently, the gut microbiome has been proposed as a CVRF, and a role in AF has been hypothesized. Our objectives were to investigate the gut microbiome composition and associated plasma metabolites in relation to AF.
Methods: We examined 63 deep-phenotyped AF patients with moderate cardiovascular risk (median age 58 years, 22% women) in a case-control design using 75 matched controls. Microbial DNA from stool was extracted and shotgun sequenced. Plasma metabolomics of 630 metabolites was performed using the Biocrates MxP® Quant 500 kit. Associations were computed controlling for potential confounding including detailed stool, nutrition, lifestyle, physical activity and environmental information.
Findings: After accounting for a broad range of potential confounders ranging from nutrition and physical activity to organ function, the abundance of distinct gut microbial genera such as Barnesiella (Cliff’s delta = -0.28) and Collinsella (Cliff’s delta = 0.27) was related to AF. A sphingolipid metabolism-dominated metabolomics pattern was seen in AF and did not strongly correlate with the observed gut microbiome signature, suggesting they constitute parallel risk factors.
Interpretation: Validating of our findings in a previously described deep-phenotyped cardiovascular disease cohort as well as a population cohort suggested that alterations of gut microbiome composition and distinct metabolic pathways are associated with the common arrhythmia AF. The discovery and in-depth characterization of relevant microbiome-metabolite-disease relations may guide future studies to identify new biomarkers, prevention strategies or therapeutic targets for AF.
Funding: The project was funded by the German Center for Cardiovascular Research (DZHK).
Declaration of Interest: RBS received consulting fees and speaker honoraria from BMS/Pfizer. All other authors do not report competing risks.
Ethical Approval: The AFHRI A study was approved by the local Ethics Committee. Informed, written consent was obtained from all participants.
Keywords: atrial fibrillation, gut microbiome, metabolomics, epidemiology
Suggested Citation: Suggested Citation