Exploring the association between gut microbiota and venous thromboembolism using a Mendelian randomization analysis

Previous observational studies have suggested a potential association between gut microbiota (GM) and venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT). However, the causal nature of this association remains uncertain due to potential confounding factors.

The summary statistics for VTE, PE, and DVT were obtained from the meta-analysis of genome-wide association studies (GWAS) conducted by the FinnGen consortium R9. The genetic data for relevant GM single nucleotide polymorphisms (SNPs) were extracted from the meta-analysis of GWAS performed by the global MiBioGen consortium. Using SNPs as instrumental variables, the inverse variance weighting (IVW) method was primarily employed to assess the bidirectional causal relationship between GM and VTE, PE, and DVT.

For the risk of VTE onset, Candidatus Solea ferrea, Ruminococcaceae UCG002, and Ruminococcaceae UCG004 were negatively correlated, while Eubacterium hallii group, Butyricimonas, and Dorea were positively correlated. For PE, Intestinimonas, an unknown genus, and Firmicutes were negatively correlated, while Veillonella, Erysipelatoclostridium, and Lentisphaerae were positively correlated. For DVT, Mollicutes, Actinobacteria, and Bifidobacteriaceae were negatively correlated, while Adlercreutzia, Collinsella, and Desulfovibrio were positively correlated. After multiple corrections using the Bonferroni method, a significant causal relationship was identified between Ruminococcaceae and VTE. Cochran's Q test was performed to evaluate instrumental variable heterogeneity (p > 0.05), MR-Egger regression analyses were performed to examine pleiotropy (p > 0.05), and leave-one-out analysis was conducted to assess the impact of each SNP on the outcome.

Specific GM may have causal effects on VTE, PE, and DVT, potentially contributing to the development of microbiota-centered therapeutic approaches and the identification of novel biomarkers for targeted preventive strategies.