Exploring Associations between Human Milk Oligosaccharides and Growth, Body Composition and Obesity Risk in Infancy and Early Childhood

项目摘要/摘要 儿童肥胖是一项重大的公共卫生挑战，通常会追溯到成年。婴儿期和早产期 童年(出生到24个月)可能是超重和肥胖发展的关键时期，早期 营养可能起到重要作用。母乳喂养对儿童肥胖具有始终如一的保护作用。 和青春期。然而，母乳中的哪些生物活性成分对婴儿有影响呢？ 代谢表型和生长大部分仍不清楚。人乳低聚糖(HMO)是关键 人乳中的生物活性成分。HMO作为母乳益生素，帮助塑造健康的婴儿肠道 微生物组。肠道微生物群组成的不平衡可能会产生功能后果， 增加体重增加和/或代谢并发症的易感性。然而，医疗保健组织之间的联系 营养成分和婴儿生长发育、身体成分和肥胖风险还没有研究过。这一差距在 知识主要源于缺乏适当的纵向队列来研究这些关联(即 可获得的母乳样本、准确的临床诊断和详细的母体表型)以及缺乏 大量队列所需的高通量HMO分析技术。我们提议的项目将解决 通过将现有数据集与来自芬兰母婴的生物库牛奶样本进行配对，这些缺陷 STEPS采用最先进的HMO分析技术。HMO的数量和组成都很高 不同女性之间的差异，我们假设(1)母乳中的HMO成分是 与婴儿期和幼儿期的生长、身体成分和肥胖风险有关，以及(2)母亲 影响HMO组成的因素。为了检验这些假设，目标1建议对个体间进行分析 母乳中HMO组成的变化及其与生长、身体组成和 台阶队列中811对母婴超重/肥胖。目标2建议确定固定和 影响HMO组成的可修改母体因素，并应用结构方程建模 确定HMO对疾病发展的直接和间接影响。利用来自 里程碑式的步骤研究和使用新的高通量技术进行HMO成分分析提供了 研究HMO产生的母体决定因素及其影响的独特而有力的机会 关于儿童健康的卫生组织。拟议的勘探项目的发现将为 疾病预防，包括(1)保健组织补充战略，目的是增加特定的“保护性” 将HMO添加到婴儿的饮食中，以降低婴儿和儿童早期肥胖的风险，以及(2)建议 关于母乳喂养母亲的饮食或生活方式的修改，以“优化”HMO的构成和丰富 特定的“保护性”HMO。

PROJECT SUMMARY / ABSTRACT Childhood obesity is a major public health challenge that often tracks into adulthood. Infancy and early childhood (birth to 24 months) may be a critical period in the development of overweight and obesity, and early nutrition may play an important role. Breastfeeding has a consistent protecting effect from obesity in childhood and adolescence. However, which of the bioactive components in human milk contribute to the effect on infant metabolic phenotype and growth remains mostly unknown. Human milk oligosaccharides (HMO) are a key bioactive component of human milk. HMO act as human milk prebiotics and help shape a healthy infant gut microbiome. An imbalance in the gut microbiome composition can have functional consequences that can increase susceptibility for weight gain and/or metabolic complications. However, associations between HMO composition and infant growth, body composition and obesity risk have not been studied. This gap in knowledge stems primarily from a lack of suitable longitudinal cohorts to study these associations (i.e. with available breast milk samples, precise clinical diagnoses, and detailed maternal phenotyping) and the absence of technology for high-throughput HMO analysis required for large cohorts. Our proposed project will address these deficiencies by pairing existing datasets and bio-banked milk samples from the Finnish mother-infant STEPS cohort with new state-of-the-art technology for HMO analysis. HMO amount and composition are highly variable between different women, and we hypothesize (1) that HMO composition in mother's milk is associated with growth, body composition and obesity risk in infancy and early childhood, and (2) that maternal factors influence HMO composition. To test these hypotheses, Aim 1 proposes to analyze inter-individual variation in HMO composition in mother's milk and evaluate associations with growth, body composition and overweight/obesity in 811 mother-infant dyads from the STEPS cohort. Aim 2 proposes to identify fixed and modifiable maternal factors that influence HMO composition and apply structural equation modeling to determine the direct and indirect effect of HMO on disease development. Leveraging resources from the landmark STEPS study and using new high-throughput technology for HMO composition analysis provides a unique and powerful opportunity to study the maternal determinants of HMO production and the effects of HMO on child health. Discoveries from the proposed exploratory project will inform new approaches for disease prevention, including (1) HMO supplementation strategies with the aim to add specific `protective' HMO to an infant's diet to reduce the risk of obesity in infancy and early childhood, and (2) recommendations on dietary or lifestyle modifications for breastfeeding mothers to `optimize' HMO composition and enrich specific `protective' HMO.