Exploring the causal relationship between gut microbiota and thromboembolism: A Mendelian randomization study

Abstract

Although several studies have indicated potential associations between gut microbiota (GM) and thromboembolic diseases, the causative role of GM in thromboembolism remains unclear. We employed two-sample Mendelian randomization (MR) analysis to investigate the potential causal association between GM and 3 thromboembolic conditions: arterial embolism and thrombosis (AET), venous thromboembolism (VTE), and pulmonary embolism (PE). Genome-wide association study datasets from MiBioGen and FinnGen were utilized, with GM serving as the exposure and thromboembolism outcomes as endpoints. Using the inverse-variance weighted approach, under conditions without heterogeneity or horizontal pleiotropy, 16 gut microbial genera were significantly associated with thromboembolic risks. Specifically, Holdemanella and the Ruminococcus gnavus group exhibited protective effects against AET, whereas Parabacteroides, Subdoligranulum, and the Eubacterium hallii group were linked to elevated AET risk. Regarding VTE, protective associations were found for Ruminococcaceae NK4A214 group, Ruminococcaceae UCG002, Ruminococcaceae UCG004, Lachnospiraceae UCG010, Sutterella, and Christensenellaceae R.7 group, while the Eubacterium rectale group showed a positive correlation with increased VTE risk. Furthermore, Defluviitaleaceae UCG011, Ruminococcaceae UCG004, Turicibacter, Lachnospiraceae UCG010, Sutterella, and Collinsella demonstrated protective effects against PE, whereas Erysipelatoclostridium was positively associated with heightened PE risk. In conclusion, this two-sample MR study suggests potential associations between GM and thromboembolic disorders. However, as none of the associations remained significant after Bonferroni correction, these findings should be regarded as exploratory and hypothesis-generating, requiring further validation in future studies.