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

探索母乳低聚糖与婴儿期和幼儿期生长、身体成分和肥胖风险之间的关联

• 批准号: 9317205
• 负责人: Lars Bode
• 金额: $ 23.26万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-04 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9317205
• 关键词: Address; Adolescence; Adult; Affect; Behavior Therapy; Birth; Body Composition; Body mass index; Breast Feeding; Characteristics; Child health care; Childhood; Complex; Data; Data Set; Development; Diet; Diet Modification; Disease; Environment; Environmental Exposure; Environmental Risk Factor; Equation; Fatty acid glycerol esters; Goals; Growth; Height; Home environment; Human; Human Milk; Individual; Infant; Knowledge; Life; Longitudinal cohort; Mediating; Metabolic; Milk Banks; Modeling; Mothers; Obesity; Oligosaccharides; Overweight; Phenotype; Play; Polysaccharides; Postpartum Period; Predisposition; Prevention; Production; Public Health; Recommendation; Resources; Risk Factors; Role; Sampling; Shapes; Statistical Models; Stress; Supplementation; Technology; Testing; Weight; Weight Gain; Woman; clinical Diagnosis; cohort; critical period; data mining; disorder prevention; early childhood; gut microbiome; high throughput technology; infancy; infant outcome; inter-individual variation; metabolic phenotype; muscle form; novel strategies; nutrition; obesity in children; obesity risk; prebiotics; stem

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.

项目总结/摘要 儿童肥胖症是一个重大的公共卫生挑战，往往跟踪到成年。婴儿期和早期 儿童期（出生至24个月）可能是超重和肥胖发展的关键时期， 营养可能发挥重要作用。母乳喂养对儿童期肥胖有一致的保护作用 和青春期然而，母乳中的哪些生物活性成分有助于对婴儿的影响 代谢表型和生长仍然是未知的。人乳低聚糖（HMO）是一种关键的 人乳的生物活性成分。HMO作为人乳益生元，帮助塑造健康的婴儿肠道 微生物组肠道微生物组组成的不平衡可能会产生功能性后果， 增加对体重增加和/或代谢并发症敏感性。然而，健康维护组织之间的联系 然而，目前还没有研究过婴儿的身体成分与婴儿生长、身体成分和肥胖风险之间的关系。中的这一空白 知识主要源于缺乏合适的纵向队列来研究这些关联（即， 可用的母乳样本，精确的临床诊断和详细的母体表型）和缺乏 高通量HMO分析的技术需要大的队列。我们的项目将解决 通过配对现有的数据集和来自芬兰母婴的生物库母乳样本， STEPS队列采用最先进的HMO分析技术。HMO的含量和成分 不同妇女之间的差异，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相关，以及（2）母亲 影响HMO组成的因素。为了验证这些假设，目标1提出分析个体间 母乳中HMO成分的变化，并评估与生长、身体组成和 在来自STEPS队列的811对母婴对中的超重/肥胖。目标2建议确定固定和 可修改的母亲因素，影响HMO组成，并应用结构方程模型， 确定HMO对疾病发展的直接和间接影响。利用来自 具有里程碑意义的STEPS研究和使用新的高通量技术进行HMO组成分析， 独特的和强大的机会，研究产妇的决定因素HMO生产和影响， HMO儿童健康从拟议的探索性项目中发现的新方法将为 疾病预防，包括（1）HMO补充战略，目的是增加特定的“保护” HMO对婴儿饮食的建议，以减少婴儿和幼儿肥胖的风险，以及（2）建议 母乳喂养母亲的饮食或生活方式改变，以“优化”HMO的组成， 具体的“保护性”保健组织。