Genetic evidence suggests gut microbiota components may influence cardiometabolic diseases partly through circulating metabolites.
Evidence
This study tested bidirectional and two-step genetic associations among gut microbiota, circulating metabolites, and coronary artery disease, type 2 diabetes, stroke, heart failure, and hypertension.
Caveat
Most microbiota and disease links were nominal or suggestive, so the inferred causal pathways and mediated fractions remain preliminary.
Simplified
The gut microbiota is associated with cardiometabolic disorders (including coronary artery disease, type 2 diabetes, stroke, heart failure, and hypertension) through the gut-heart or gut-brain axis, among which metabolic processes play crucial roles. However, the exact causal mechanisms remain unknown. Our study sought to uncover the causal relationships between the gut microbiota, circulating metabolites and cardiometabolic diseases via (MR) analysis. Forward MR was utilized to investigate the causal effects of the gut microbiota and circulating metabolites on the risk of cardiometabolic diseases. Reverse MR was subsequently performed to analyze the significant gut microbiota and circulating metabolites. Two-step MR was employed to examine the impact of circulating metabolites on the relationship between the gut microbiota and cardiometabolic diseases and to determine the mediated fractions. Our results revealed a nominal causal relationship with 23, 23, 22, 20, and 19 gut microbiota constituents for coronary artery disease, type 2 diabetes, stroke, heart failure, and hypertension, respectively. We also identified 2 significant associations and 13 suggestive associations between circulating metabolites and these cardiometabolic diseases. Reverse MR analysis revealed that genetically predicted type 2 diabetes was suggestively associated with 3 circulating metabolites, whereas stroke demonstrated a suggestive association with 3 distinct gut microbiota. Further screening identified 4 circulating metabolites as potential mediators in the pathway from the gut microbiota to cardiometabolic diseases. Our study revealed a causal link between gut microbiome components and cardiometabolic diseases and that circulating metabolites potentially act as intermediaries in this association.
Key numbers
23
Gut Microbiota Related to Coronary Artery Disease
Number of gut microbiota associated with coronary artery disease.
23
Gut Microbiota Related to Type 2 Diabetes
Number of gut microbiota associated with type 2 diabetes.
4
Circulating Metabolites as Potential Mediators
Number of circulating metabolites identified as potential mediators.
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