Effects of Gut Microbiota and Metabolites on Heart Failure and Its Risk Factors: A Two-Sample Mendelian Randomization Study

IntroductionPrevious observational studies have indicated that gut microbiota and metabolites may contribute to heart failure and its risk factors. However, with the limitation of reverse causality and confounder in observational studies, such relationship remains unclear. This study aims to reveal the causal effect of gut microbiota and metabolites on heart failure and its risk factors. MethodsThis study collected summary statistics regarding gut microbiota and metabolites, heart failure, diabetes, hypertension, chronic kidney disease, myocardial infarction, atrial fibrillation, hypertrophic cardiomyopathy, dilated cardiomyopathy, coronary heart disease, valvular heart disease, and myocarditis. Two-sample Mendelian randomization analysis was performed using MR-Egger, inverse variance weighted (IVW), MR-PRESSO, maximum likelihood, and weighted median. ResultsResults from gene prediction showed that among all gut microbiota, candida, shigella, and campylobacter were not associated with higher incidence of heart failure. However, genetic prediction suggested that for every 1 unit increase in shigella concentration, the relative risk increased by 38.1% for myocarditis and 13.3% for hypertrophic cardiomyopathy. Besides, for every 1 unit increased in candida concentration, the relative risk of chronic kidney disease increased by 7.1%. As for intestinal metabolites, genetic prediction results suggested that for every 1 unit increase in betaine, the relative risk of heart failure and myocardial infarction increased by 1.4% and 1.7%, separately. ConclusionsThis study suggested new evidence of the relationship between gut microbiota and heart failure and its risk factors, which may shed light on designing microbiome- and microbiome-dependent metabolite interventions on heart failure and its risk factors in clinical trials in the future.

Automated summary

This study used Mendelian randomization analysis to reveal the causal effect of gut microbiota and metabolites on heart failure and its risk factors. The results showed that candida and campylobacter were not associated with higher incidence of heart failure, while increasing concentration of shigella was associated with higher risks of myocarditis and hypertrophic cardiomyopathy. In addition, increased concentration of candida was associated with higher risk of chronic kidney disease, and betaine was associated with higher risks of heart failure and myocardial infarction.