Balan Preethi, Zhang Junfeng, Tan Kok Hian, Cooray Upul, Lee Ryan Wk, Ong Mah Lay, Seneviratne Chaminda Jaya
Singapore Oral Multiomics Initiative, National Dental Research Institute Singapore (NDRIS), National Dental Centre, Singapore, Singapore.
Oral Health ACP, Duke NUS Medical School, Singapore, Singapore.
Int J Oral Sci. 2025 Jul 22;17(1):55. doi: 10.1038/s41368-025-00390-8.
Chemical exposure during prenatal development has significant implications for both maternal and child health. Compared to blood, saliva is a non-invasive and less resource-intensive, alternative. Given the temporal variability of xenobiotic metabolites (XM), repeated sampling is essential. Therefore, saliva offers a valuable tool for the longitudinal assessment of prenatal exposomes. Despite its potential, no studies have explored saliva for XM measurement. This study pioneered using saliva to assess XM detectability and investigate the associations between prenatal XM and endogenous metabolomes in pregnant women. Saliva samples were analysed using mass spectrometry from 80 pregnant women at 24-34 weeks gestation. Metabolomes and exposomes were annotated using the Human Metabolome and U.S. Environmental Protection Agency databases. Metabolome-XM associations were clustered using Glay community clustering. Linear regression models, adjusted for age, estimated associations between catecholamines and XMs. XM levels were validated in a cohort of women (n = 14) with and without preeclampsia. Our study identified 582 metabolomes and 125 XM in saliva, demonstrating its potential as a matrix for exposure measurement. After false discovery rate correction, 18 109 significant metabolome-XM associations were identified. Community clustering revealed 37 connected clusters, with the largest cluster (238 nodes) enriched in tyrosine and catecholamine metabolism. Food-contact-chemicals and food-additives were significantly associated with higher catecholamine and their metabolite levels. Subgroup analyses revealed higher concentrations of these chemicals in women with preeclampsia compared to healthy controls. This study demonstrates that saliva contains valuable molecular data for measuring exposomes. Food-related chemicals were associated with higher catecholamine levels, which may be relevant to the prevalence of hypertensive crises in pregnancy.
孕期化学物质暴露对母婴健康都有重大影响。与血液相比，唾液是一种非侵入性且资源消耗较少的替代物。鉴于外源性代谢物（XM）的时间变异性，重复采样至关重要。因此，唾液为产前暴露组的纵向评估提供了一个有价值的工具。尽管有其潜力，但尚未有研究探索用唾液测量XM。本研究率先使用唾液评估XM的可检测性，并调查孕妇产前XM与内源性代谢组之间的关联。在妊娠24 - 34周时，对80名孕妇的唾液样本进行了质谱分析。使用人类代谢组和美国环境保护局数据库对代谢组和暴露组进行注释。使用Glay社区聚类对代谢组 - XM关联进行聚类。线性回归模型在调整年龄后，估计儿茶酚胺与XM之间的关联。在一组有和没有先兆子痫的女性（n = 14）中对XM水平进行了验证。我们的研究在唾液中鉴定出582种代谢组和125种XM，证明了其作为暴露测量基质的潜力。经过错误发现率校正后，鉴定出18109个显著的代谢组 - XM关联。社区聚类揭示了37个相连的聚类，最大的聚类（238个节点）富含酪氨酸和儿茶酚胺代谢。食品接触化学品和食品添加剂与较高的儿茶酚胺及其代谢物水平显著相关。亚组分析显示，与健康对照组相比，先兆子痫女性中这些化学品的浓度更高。本研究表明，唾液包含用于测量暴露组的有价值的分子数据。与食物相关的化学品与较高的儿茶酚胺水平相关，这可能与孕期高血压危机的患病率有关。
