Abstract
BACKGROUND: Gestational diabetes mellitus (GDM) is associated with adverse pregnancy outcomes. The oral microbiota, influenced by genetic factors, may play a role in GDM development, but the causal association remains unclear. METHODS: We employed a two-sample Mendelian randomization (MR) approach using Genome-Wide Association Study (GWAS) data on GDM from FINN cohort data (ID: finngen_R10_GEST_DIABETES) and GWAS data on the Oral microbiota from the Danish ADDITION-PRO cohort. We screened SNPs significantly associated with Oral microbiota abundance as instrumental variables (IVs) and assessed their association with GDM risk. The study primarily used an inverse variance weighting (IVW) approach and further applied MR-Egger regression, weighted median, and weighted mode methods for robustness testing. Sensitivity analyses were conducted to evaluate the impact of heterogeneity and pleiotropy, including MR-Egger, MR-PRESSO, Cochran's Q, and leave-one-out methods. RESULTS: We identified 267 IVs associated with Oral microbiota abundance. IVW analysis revealed a positive causal association between Genus Schaalia and GDM risk (OR = 1.03, 95% CI: 1.01-1.06, P = 0.02) and a negative association between Genus Haemophilus and GDM risk (OR = 0.96, 95% CI: 0.93-1.00, P = 0.034). Sensitivity analyses confirmed the robustness of these two results, showing no evidence of heterogeneity or pleiotropy. CONCLUSION: Our study provides evidence for a causal association between Genus Schaalia and Haemophilus and GDM risk. This highlights the potential role of the Oral microbiota in GDM pathogenesis and suggests potential targets for GDM prevention and treatment.