Associations of Plasma Gut Microbiota-Derived TMAO and Precursors in Early Pregnancy with Gestational Diabetes Mellitus Risk: A Nested Case-Control Study

作者：Yani Wu, He Bai, Ying Lü, Ruiheng Peng, Mingxia Qian, Xuchen Yang, Enmao Cai, Wenli Ruan, Qianlong Zhang, Jun Zhang, Liqiang Zheng, on behalf of the Shanghai Birth Cohort · 发表于：Nutrients · 年份：2025 · DOI：10.3390/nu17050810 · 被引用次数：5 · 研究领域：Gestational Diabetes Research and Management、Bariatric Surgery and Outcomes、Adolescent and Pediatric Healthcare

Objectives: Gut microbiota-derived metabolites—trimethylamine N-oxide (TMAO) and its precursors choline, betaine, and carnitine—have been linked to various health outcomes. However, their role in gestational diabetes mellitus (GDM) remains unclear due to inconsistent findings. This study aims to investigate the associations between maternal plasma concentrations of these metabolites during early pregnancy and the risk of GDM. Methods: A nested case–control study was performed in the Shanghai Birth Cohort. GDM cases and non-GDM controls were matched according to maternal age at a ratio of 1:4. Three hundred twenty-one identified GDM cases and 1284 controls were included. Maternal plasma concentrations of TMAO and its precursors were measured between 12 and 16 weeks of gestation in early pregnancy using high-performance liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were applied to assess associations between metabolite levels and GDM risk and to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Multivariate linear regressions evaluated relationships between metabolite concentrations and glycemic indicators. Stratified and sensitivity analyses were conducted to ensure robustness. Results: Maternal plasma levels of TMAO, choline, betaine, and carnitine in early pregnancy were 1.95 μmol/L (IQR, 1.16–3.20), 9.25 μmol/L (IQR, 7.31–11.98), 20.51 μmol/L (IQR, 16.92–24.79), and 17.13 μmol/L (IQR, 13.33–21.16), respectively. B...