Investigating the association between gut microbiota and venous thromboembolism mediated by immune cells: A mediation Mendelian randomization study

Recent studies have indicated a correlation between gut microbiota (GM) and venous thromboembolism (VTE). However, the specific effects of GM on VTE-related immune factors remain largely unknown. Thus, we conducted a Mendelian randomization (MR) analysis to explore the relationships between GM, immune cells, and VTE. This mediation MR study utilized the summary-level data of respective genome-wide association study for 207 taxa and 205 bacterial pathways, 731 immune cell traits, and VTE. This MR design was deployed, and comprehensive sensitive analyses were followed to validate the robustness of the results. We used the inverse-variance weighted, Bayesian-weighted MR, MR-Egger regression, MR-Egger intercept test, Cochrane Q test, and leave-one-out analysis as the primary methods. We identified a suggestive association between 16 bacterial traits and VTE risk, with 3 taxa affecting VTE through 2 types of immune cells as mediators. For example, "c_Bacteroidia" was implicated in reducing the risk of VTE via "DN (CD4- CD8-) NKT % lymphocyte" cells. This study suggested the role of the specific GMs on the VTE risk, emphasizing the potential mediatory function of GM-related immune cells.