Gut microbiota as a residual risk factor causally influencing cardiac structure and function: Mendelian randomization analysis and biological annotation.

Background: The gut microbiota (GM) is widely acknowledged to have a significant impact on cardiovascular health and may act as a residual risk factor affecting cardiac structure and function. However, the causal relationship between GM and cardiac structure and function remains unclear. Objective: This study aims to employ a two-sample Mendelian randomization (MR) approach to investigate the causal association between GM and cardiac structure and function. Methods: Data on 119 GM genera were sourced from a genome-wide association study (GWAS) meta-analysis (13,266 European participants) conducted by the MiBioGen consortium, while data on 16 parameters of cardiac structure and function were obtained from the UK Biobank's GWAS of cardiac magnetic resonance imaging (up to 41,135 European participants). Inverse variance weighted (IVW), MR-Egger, and weighted median (WM) methods were utilized for causal association assessments, with sensitivity analyses conducted to reinforce the findings. Finally, biological annotation was performed on the GWAS data of GM and cardiac phenotypes with causal associations to explore potential mechanisms. Results: The MR analysis, predominantly based on the IVW model, revealed 93 causal associations between the genetically predicted abundance of 44 GM genera and 16 cardiac structure and function parameters. These associations maintained consistent directions in MR-Egger and WM models, with no evidence of pleiotropy detected. Biological annotations suggest that GM may influence cardiac structure and function through pathways involved in myocardial cell development, cardiac contractility, and apoptosis. Conclusion: The MR analysis supports a causal association between certain abundances of genetically predicted GM and cardiac structure and function, suggesting that GM could be a residual risk factor impacting cardiac phenotypes.