Jin Hui, Wang Yapei, Li Hongbin, Cheng Yinqin, Ma Yumin
Department of Internal Medicine, The Second People's Hospital of Nantong, Nantong, 226000, People's Republic of China.
Int J Womens Health. 2025 Aug 30;17:2777-2791. doi: 10.2147/IJWH.S531088. eCollection 2025.
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.
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.
We identified 267 IVs associated with Oral microbiota abundance. IVW analysis revealed a positive causal association between Genus and GDM risk (OR = 1.03, 95% CI: 1.01-1.06, P = 0.02) and a negative association between Genus 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.
Our study provides evidence for a causal association between Genus and and GDM risk. This highlights the potential role of the Oral microbiota in GDM pathogenesis and suggests potential targets for GDM prevention and treatment.
妊娠期糖尿病（GDM）与不良妊娠结局相关。受遗传因素影响的口腔微生物群可能在GDM的发生发展中起作用，但因果关系仍不明确。
我们采用两样本孟德尔随机化（MR）方法，使用来自芬兰队列数据（ID：finngen_R10_GEST_DIABETES）的GDM全基因组关联研究（GWAS）数据和丹麦ADDITION-PRO队列的口腔微生物群GWAS数据。我们筛选出与口腔微生物群丰度显著相关的单核苷酸多态性（SNPs）作为工具变量（IVs），并评估它们与GDM风险的关联。该研究主要使用逆方差加权（IVW）方法，并进一步应用MR-Egger回归、加权中位数和加权模式方法进行稳健性检验。进行敏感性分析以评估异质性和多效性的影响，包括MR-Egger、MR-PRESSO、 Cochr an's Q和留一法。
我们鉴定出267个与口腔微生物群丰度相关的IVs。IVW分析显示某属与GDM风险之间存在正因果关联（OR = 1.03，95%CI：1.01-1.06，P = 0.02），另一属与GDM风险之间存在负关联（OR = 0.96，95%CI：0.93-1.00，P = 0.034）。敏感性分析证实了这两个结果的稳健性，未显示异质性或多效性的证据。
我们的研究为某属与另一属和GDM风险之间的因果关联提供了证据。这突出了口腔微生物群在GDM发病机制中的潜在作用，并提示了GDM预防和治疗的潜在靶点。
