Causal effects between gut microbiota and coronary heart disease: A Mendelian randomization study

Therapeutic interventions targeting gut microbiota (GM) are promising strategies for the prevention and treatment of coronary heart disease (CHD). Numerous studies have demonstrated a correlation between the GM and CHD. However, these findings do not describe a causal relationship between GM and CHD. Using a bidirectional 2-sample Mendelian Randomization (MR) analysis approach, we utilized a genome-wide association study dataset from the MiBioGen Consortium (N = 18,340) and CHD data from the CARDIoGRAMplusC4D 1000 Genome-based genome-wide association study meta-analysis (60,801 cases and 123,504 controls) to investigate the causal link between GM and CHD. Methods such as inverse-variance weighted, MR-Egger, weighted median, and weighted mode were used to assess causality. Sensitivity analyses, including Cochran Q statistic, MR-Egger intercept, MR-PRESSO global test, and leave-one-out analysis, were used to detect heterogeneity and horizontal pleiotropy. Furthermore, a reverse MR analysis was performed to evaluate the potential for reverse causality. The genus Butyricicoccus and order Victivallales demonstrated a significant protective effect against CHD at the locus-wide significance level, whereas the genera Clostridium (innocuum species), Oxalobacter, and Turicibacter were associated with an increased risk of CHD. The sensitivity analysis did not yield any substantial indications of pleiotropy or heterogeneity. We describe a simultaneous cause-and-effect relationship between GM and CHD, and expand the range of bacterial taxa that exhibit a causal connection with CHD. These bacterial taxa can serve as innovative biomarkers to facilitate targeted therapeutic interventions for CHD and enhance our understanding of the intricate "gut-heart axis."