Association between gut microbiota and venous thromboembolism: a two-sample Mendelian randomization study

Abstract

Abstract Background: Recent studies have suggested an association between gut microbiota (GM) and venous thromboembolism (VTE). However, observational studies cannot indicate causality and population-level studies with a higher evidence level for causality are lacking. Therefore, our study aimed to explore the causal association of GM with VTE. Methods: This study utilized the summary-level data of respective genome-wide association study for 196 gut microbial taxa and VTE. Two-sample Mendelian randomization (MR) design was deployed and comprehensively sensitive analyses were followed to validate the robustness of results. We used the inverse-variance weighted (IVW) method, the weighted median method, weighted mode method, simple mode method, MR-Egger regression, MR-Egger intercept test, Cochrane’s Q-test, outlier test, and leave-one-out analysis as the primary analysis. Results: We identified suggestive associations between 17 bacterial traits and the risk of VTE. Porphyromonadaceae (IVW odds ratio (OR): 1.3729, p=0.0035) and Cyanobacteria (IVW OR: 1.2151, p=0.0048) were associated with increased risk of VTE. Three gut microbiota taxa (Eubacteriumrectalegroup (IVW OR: 1.0038, p=0.0278), Coprococcus2 (IVW OR: 1.0041, p = 0.0063), and LachnospiraceaeUCG001 (IVW OR: 1.0041, p=0.0009) were predicted to play a causal role in enhancing the risk of encompassing deep vein thrombosis. And three gut microbiota taxa (Christensenellaceae (IVW OR: 1.0023, p=0.0497), Streptococcaceae (IVW OR: 1.0031, p=0.0279), Victivallaceae (IVW OR: 1.0014, p=0.0493) were positively associated with pulmonary embolism. Conclusions: This study suggested the role of the specific GM on the risk for VTE, which may provide new ideas and a theoretical basis for the prevention and treatment of VTE in the future.