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.”