biostudies-literatureCheng PFNoncommunicable Chronic Diseases-National Science and Technology Major Project97https://www.ebi.ac.uk/biostudies/studies/S-EPMC12181570biostudies-literatureUnknown15(1)Emerging evidence links gut microbiota (GM) to venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE), but causal insights are limited. Using two-sample Mendelian randomization (MR), we assessed causal effects of 211 GM taxa and 489 plasma metabolites on VTE/DVT/PE. Genetic instruments (single nucleotide polymorphism) for GM and metabolites were leveraged to infer causality, complemented by mediation and pathway analyses. Sixteen GM taxa (e.g., protective Firmicutes, Clostridia; risk-enhancing Bacteroidetes, Desulfovibrionaceae) and 40 metabolites showed causal associations with VTE/DVT/PE. Reverse MR identified 11 GM changes secondary to thrombosis. No pleiotropy or heterogeneity was detected. Ten metabolite-mediated pathways (e.g., arginine biosynthesis) bridged GM to thrombosis, suggesting GM-metabolite interactions as potential biomarkers for thrombotic risk stratification and prognosis.AMB ExpressGut microbiota, plasma metabolites, and venous thromboembolism: a Mendelian randomization study.PMC121815702023ZD0502400Cheng PFWu JSLi GMWang JXfalseGut microbiota, plasma metabolites, and venous thromboembolism: a Mendelian randomization study.Emerging evidence links gut microbiota (GM) to venous thromboembolism (VTE), deep vein thrombosis (DVT), and pulmonary embolism (PE), but causal insights are limited. Using two-sample Mendelian randomization (MR), we assessed causal effects of 211 GM taxa and 489 plasma metabolites on VTE/DVT/PE. Genetic instruments (single nucleotide polymorphism) for GM and metabolites were leveraged to infer causality, complemented by mediation and pathway analyses. Sixteen GM taxa (e.g., protective Firmicutes, Clostridia; risk-enhancing Bacteroidetes, Desulfovibrionaceae) and 40 metabolites showed causal associations with VTE/DVT/PE. Reverse MR identified 11 GM changes secondary to thrombosis. No pleiotropy or heterogeneity was detected. Ten metabolite-mediated pathways (e.g., arginine biosynthesis) bridged GM to thrombosis, suggesting GM-metabolite interactions as potential biomarkers for thrombotic risk stratification and prognosis.2025-01-01T00:00:00Z2025 Jun2026-06-03T07:46:38.764Z2026-04-26T03:10:05.607ZS-EPMC121815704054014310.1186/s13568-025-01903-8