HDHL-Biomarkers: Early life programming of childhood health: a nutritional and epigenetic investigation (ALPHABET)

近几十年来，肥胖、心脏代谢疾病、哮喘、骨质疏松症和神经发育障碍的患病率不断上升，不能完全用遗传或成人生活方式因素来解释。越来越多的证据表明与早期生活环境因素有关。如果存在这样的联系，那么一定有非遗传机制保留了早期生活暴露的记忆，如怀孕期间或幼儿期的不理想营养，并影响几十年后的健康。DNA甲基化，即在DNA上添加甲基，已被认为是一种可能的机制，因为它对环境有反应并影响基因表达。孕妇怀孕期间的饮食是一种可改变的行为，可能影响孕产妇、新生儿和儿童的健康。然而，怀孕期间对最佳胎儿生长发育的具体饮食要求在很大程度上是未知的，因为对健康的影响在接触后几十年才开始显现。然而，DNA甲基化模式应该几乎立即受到影响，如果它们与以后的健康结果有关，则应该终生保留。该项目将利用现有欧洲纵向出生队列的生物样本和数据，调查从出生到童年到成年，由饮食质量和炎症潜力指数总结的母亲饮食、健康结果和DNA甲基化模式之间的复杂关系。因此，我们将能够观察产前饮食如何改变婴儿DNA甲基化模式，以及这些改变是否以及如何在整个生命中保持，并与成年期的健康结果相关。这些观察结果可能有助于制定更精细的饮食建议，以促进一生的最佳健康。

The rising prevalence of obesity, cardiometabolic disease, asthma, osteoporosis and neurodevelopmental disorders over recent decades cannot be fully explained by genetic or adult lifestyle factors. Increasing evidence suggests links to early life environmental factors. If such links exist, then there must be non-genetic mechanisms that retain memory of early life exposures such as suboptimal nutrition during pregnancy or early childhood and that influence health decades later. DNA methylation, the addition of methyl groups to DNA, has been proposed as a possible mechanism because it is responsive to the environment and influences gene expression. Maternal diet during pregnancy is a modifiable behaviour that could impact on maternal, neonatal and child health. However the specific dietary requirements during pregnancy for optimal fetal growth and development are unknown in large part because effects on health only begin to appear decades after exposure. DNA methylation patterns however should be affected almost immediately and, if they are linked to later health outcomes, should remain throughout life. This project will utilise biological samples and data from existing European longitudinal birth cohorts to investigate the complex relationships between maternal diet summarised by indices of diet quality and inflammatory potential, health outcomes and DNA methylation patterns from birth throughout childhood and into adulthood. Hence, we will be able to observe how prenatal diet modifies infant DNA methylation patterns and if and how these modifications are maintained throughout life and relate to health outcomes in adulthood. These observations may aid development of more refined dietary recommendations for promoting optimal health throughout life.