Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
Front Public Health. 2023 Oct 11;11:1248609. doi: 10.3389/fpubh.2023.1248609. eCollection 2023.
The relationship between pesticide exposures and metabolomics biomarkers is not well understood. We examined the changes in the serum metabolome (early biomarkers) and the metabolic pathways associated with various pesticide exposure scenarios (OPE: overall exposure, PEM: exposure in months, PEY: exposure in years, and PEU: reported specific pesticides use) using data from the Northern Finland Birth Cohort 1966 31-year cross-sectional examination. We utilized questionnaire data on pesticide exposures and serum samples for nuclear magnetic resonance (NMR)-based metabolomics analyses. For exposures and metabolites associations, participants size varied between 2,361 and 5,035. To investigate associations between metabolomics biomarkers and exposure to pesticide scenarios compared to those who reported no exposures multivariable regression analyses stratified by sex and adjustment with covariates (season of pesticide use, socioeconomic position (SEP), alcohol consumption, BMI, and latitude of residence) were performed. Multiple testing by Benjamini-Hochberg false discovery rate (FDR) correction applied. Pesticide exposures differed by sex, season of pesticide use, alcohol, SEP, latitude of residence. Our results showed that all pesticide exposure scenarios were negatively associated with decreased HDL concentrations across all lipoprotein subclasses in women. OPE, PEY, and PEU were associated with decreased branched-chain amino acid concentrations in men and decreased albumin concentrations in women. OPE, PEY and PEU were also associated with changes in glycolysis metabolites and ketone bodies in both sexes. Specific pesticides exposure was negatively associated with sphingolipids and inflammatory biomarkers in men. In women, OPE, PEM, and PEU were associated with decreased apolipoprotein A1 and increased apolipoprotein B/apolipoprotein A1 ratio. Our findings suggest that identification of early biomarkers of disease risk related to pesticide exposures can inform strategies to reduce exposure and investigate causal pathways. Women may be more susceptible to non-occupational pesticide exposures when compared to men, and future sex-specific studies are warranted.
农药暴露与代谢组学生物标志物之间的关系尚未得到很好的理解。我们利用来自芬兰北部出生队列 1966 年 31 年的横断面研究的数据，检查了血清代谢组（早期生物标志物）和与各种农药暴露情况相关的代谢途径的变化（OPE：总体暴露，PEM：暴露月数，PEY：暴露年数，PEU：报告的特定农药使用）。我们利用了关于农药暴露的问卷数据和基于核磁共振（NMR）的代谢组学分析的血清样本。对于暴露和代谢物的关联，参与者的大小在 2361 到 5035 之间变化。为了研究代谢组学生物标志物与农药暴露情况之间的关联，与报告没有暴露的参与者相比，我们进行了多变量回归分析，按性别分层，并进行了协变量调整（农药使用季节、社会经济地位（SEP）、酒精消耗、BMI 和居住纬度）。应用贝叶斯错误发现率（FDR）校正进行了多重检验。农药暴露因性别、农药使用季节、酒精、SEP、居住纬度而不同。我们的结果表明，所有农药暴露情况都与女性所有脂蛋白亚类中 HDL 浓度降低有关。OPE、PEY 和 PEU 与男性支链氨基酸浓度降低和女性白蛋白浓度降低有关。OPE、PEY 和 PEU 也与两性糖酵解代谢物和酮体的变化有关。特定农药暴露与男性的鞘脂和炎症生物标志物呈负相关。在女性中，OPE、PEM 和 PEU 与载脂蛋白 A1 降低和载脂蛋白 B/载脂蛋白 A1 比值升高有关。我们的研究结果表明，识别与农药暴露相关的疾病风险的早期生物标志物可以为减少暴露和研究因果途径提供信息。与男性相比，女性可能更容易受到非职业性农药暴露的影响，因此需要进行未来的性别特异性研究。
