Altered Gut Microbiota as a Potential Risk Factor for Coronary Artery Disease in Diabetes: A Two-Sample Bi-Directional Mendelian Randomization Study

Abstract

Abstract Background Alterations in the gut microbiota are closely associated with type 2 diabetes(T2D) and its complications, specifically coronary artery disease (CAD). However, the causal relationship between gut microbiota and diabetic coronary artery disease (DCAD) remains unknown. Methods We conducted two-sample bidirectional Mendelian randomization (MR) causality analyses using data from the DIAGRAM, GERA, UKB, FHS, and mibioGen cohorts. By filtering the genome-wide association study (GWAS) databases for type 2 diabetes, coronary artery disease, gut microbiota, and metabolites, we explored potential connections between the gut microbiota and DCAD. Results Oxalobacter formigenes was found to be causally correlated with both T2D and CAD. Every 10-unit increase in host genetic-dependent T2D risk increases the risk of increased family Oxalobacteraceae (Beta = 0.061, 95% CI = 0.002, 0.119) abundance by 6.1%. Each 10-unit increase in the abundance of genus Oxalobacter (Beta = 0.082, 95% CI = 0.026, 0.137) increased the risk of host genetic CAD in the host by 8.2%. This is potentially an important pathway by which T2D increases the risk of CAD by influencing the gut microbiota. The risk of CAD associated with Methanobacteria, providing direction for research on mechanisms underlying trimethylamine N-oxide (TMAO) and the causal role of carnitine in preventing the development of CAD. In addition, provided evidence for a causal relationship between elevated proline, lysophosphatidylcholine, asparagine and salicylurate and T2D as well as CAD. Conclusions The sensitivity analysis of study offers compelling evidence that alterations in the Oxalobacter formigenes are probably a risk for DCAD, and that DCAD also affects the abundance of parts of the gut microbiota. Increased blood TMAO concentrations in patients with CAD are potentially associated decreased abundance of methanogens.