Association of the gut microbiota with coronary artery disease and myocardial infarction: A Mendelian randomization study

Abstract

Background: Previous studies have indicated that the gut microbiota (GM) is associated with coronary artery disease (CAD), but the causality of these associations remains unestablished due to confounding factors and reverse causality. We conducted Mendelian randomization study (MR) to determine the causal effect of the specific bacterial taxa on CAD/myocardial infarction (MI) and identify the mediating factors involved.Methods: Two-sample MR, multivariable MR (MVMR) and mediation analysis were performed. Inverse-variance weighting (IVW) was the main method used to analyze causality, and sensitivity analysis was used to verify the reliability of the study. Causal estimates from CARDIoGRAMplusC4D and FinnGen databases were combined using the meta-analysis method, and repeated validation was conducted based on the UK Biobank (UKB) database. Confounders that may affect the causal estimates were corrected by MVMP and the potential mediation effects were investigated by using mediation analysis.Results: The study suggested that increased abundance of the RuminococcusUCG010 genus leads to a lower risk of CAD (OR, 0.88; 95% CI, 0.78, 1.00; p = 2.88 × 10−2) and MI (OR, 0.88; 95% CI, 0.79, 0.97; p = 1.08 × 10−2), with consistent results in both meta-analysis (CAD: OR, 0.86; 95% CI, 0.78, 0.96; p = 4.71 × 10−3; MI: OR, 0.82; 95% CI, 0.73, 0.92; p = 8.25 × 10−4) and repeated analysis of the UKB dataset (CAD: OR, 0.99; 95% CI, 0.99, 1.00, p = 2.53 × 10−4; MI: OR, 0.99; 95% CI, 0.99, 1.00, p = 1.85 × 10–11). Based on multiple databases, T2DM was proved as a mediating factor in the causal effect of RuminococcusUCG010 and CAD/MI, with an average mediation effect proportion of 20% on CAD and 17% on MI, respectively.Conclusion: This MR study provided suggestive genetic evidence that the higher the RuminococcusUCG010 abundance is, the lower the risk of CAD and MI, with T2DM playing a mediating effect. This genus may become a novel target in strategies for treating and preventing CAD and MI.

Plant-based diet and its effect on coronary artery disease: A narrative review

“…The gut microbiota is a complex and diverse community of microorganisms that inhabits the gastrointestinal tract and plays a crucial role in regulating metabolism, immunity, and inflammatory processes. Additionally, recent research has revealed that the bacteria in atherosclerotic plaques are analogous to those that colonize the gut[ 51 ]. One of the metabolites produced by the gut microbiota is trimethylamine-N-oxide (TMAO)[ 4 ], which is derived from dietary sources such as choline, betaine, and L-carnitine.…”

“…One of the metabolites produced by the gut microbiota is trimethylamine-N-oxide (TMAO)[ 4 ], which is derived from dietary sources such as choline, betaine, and L-carnitine. TMAO has been linked to the development and progression of CAD due to its pro-inflammatory effects and its inhibition of reverse cholesterol transport[ 51 ]. With their higher intake of red meat, Omnivores are significantly more susceptible to CVD than those who consume PBDs.…”

“…The primary treatment for sitosterolemia is a combination of a diet that is low in plant sterols and the use of the medication ezetimibe, which inhibits cholesterol absorption in the intestines. This treatment is highly effective in reducing the levels of plant sterols in the blood and is considered the first-line therapy for this condition[ 51 ].…”

Intestinal microbiota and tuberculosis: Insights from Mendelian randomization

“…To ensure adequate selection of IVs, SNPs with P values below the genome-wide significance threshold (1 × 10 -5 ) were chosen. According to previous research, [ 16 , 17 ] the LD parameter (r 2 ) for SNPs was set at 0.001, with a genetic distance of 10000 kb, to examine the independence of variables and LD effects. The PhenoScanner website was subsequently utilized in January 2024 to check for associations between IVs and potential confounders, such as smoking and alcohol consumption.…”

Gut microbiota in combination with blood metabolites reveals characteristics of the disease cluster of coronary artery disease and cognitive impairment: a Mendelian randomization study

“…Nowadays, large-scale GWAS data on gut microbiota, blood metabolites, CAD, and cognitive impairment are publicly available, creating opportunities for us to investigate the causal associations between gut microbiota, blood metabolites, and the disease cluster of CAD combined with cognitive impairment through MR. Previously, some researchers have found causal links between specific gut microbiota and CAD and Alzheimer's disease (AD) by MR, and others have explored causal links between blood metabolites and AD by MR (21)(22)(23), but they have not gone further to explore the causal links between the gut microbiota and the blood metabolites in patients with CAD as well as AD, and they have not focused their attention on the disease cluster of CAD combined with cognitive impairment. Therefore, we will conduct a more comprehensive and in-depth exploration by MR to provide new insights into biomarkers and treatments for the disease cluster of CAD combined with cognitive impairment.…”