Causal relationship between gut microbiota and metabolic syndrome: A bidirectional Mendelian randomization study

Metabolic syndromes (MetS) are complex metabolic disorders, the pathogenesis of which has not been fully elucidated. In recent years, the association between the gut microbiota and MetS has attracted widespread attention, but the causal relationship remains unclear. We performed a 2-sample Mendelian randomization analysis (MR) to examine whether the gut microbiota is causally related to MetS and its components to find a basis for potential diagnostic or intervention approaches for MetS. We utilized summary statistics from whole-genome association analyses of gut microbiota from the MiBioGen consortium and obtained MetS-related data from the UK Biobank, IEU Open GWAS project, and The Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC). MR analyses were performed using inverse variance weighted, MR-Egger, and weighted median. Sensitivity analyses were conducted to verify the robustness of the results. Among the 211 gut microbiota, we identified 8 that were significantly associated with the risk of MetS. Specifically, Lachnospiraceae (family), Veillonellaceae (family), Victivallaceae (family), Odoribacter (genus), and Olsenella (genus) may increase the risk of MetS, while Bifidobacteriaceae (family), Ruminococcaceae UCG-010 (genus), Actinobacteria (phylum) may decrease the risk of MetS. Additionally, we discovered that multiple microbiota are associated with various components of MetS, such as BMI, hypertension, and blood lipid levels. This study is the first to use MR methods to reveal the potential causal relationship between specific gut microbiota and MetS, providing a new perspective for understanding the pathogenesis of MetS, and offering important evidence for the development of gut microbiota-based prevention and treatment strategies for MetS.