Dietary influence on infant growth and the gut microbiota

该项目的总体目标是确定不同富含蛋白质食物的婴儿饮食如何调节生长轨迹和肠道微生物区系的发育。美国国立卫生研究院和美国农业部目前都在解决生命早期对循证饮食指导的迫切需要，特别是关于蛋白质摄入量，但在早期补充喂养期间，富含蛋白质的食物对生长和发育的影响存在显著的知识差距。早期补充喂养(约5至12个月大)，当婴儿开始食用母乳或配方奶粉以外的食物时，是发育可塑性的关键过渡期。在这一关键时期，肠道微生物区系的生长轨迹和变化有可能规划长期的体重、组成和疾病风险，并受到饮食的很大影响。我们对配方奶粉喂养的婴儿进行的初步研究数据表明，高摄入量的肉类和乳制品两种富含蛋白质的食物会导致5到12个月大的婴儿有不同的生长模式。一个重要的初步发现是，以肉类和乳制品为基础的食物在12个月时直接影响肠道微生物区系的多样性、组成和短链脂肪酸的产生。肠道微生物区系组成的变化也与婴儿的线性生长(长度增长)有关。在这里，我们提出了三个具体目标，以确定在随机对照试验中，常见富含蛋白质食品的引入如何影响婴儿生长(目标1)，肠道微生物区系的发育(目标2)以及肠道微生物区系与婴儿生长之间的关系(目标3)。健康的足月儿(n=300)将被招募并随机分为肉类、乳制品、植物性饮食组或参照组(标准护理)，从5个月到12个月。我们将使用控制喂养(所有提供的食物，如果需要的话，也可以使用配方奶)，并对肠道微生物区系、婴儿生长、血液生物标记物(IGF-1、IGFBP3、胰岛素、氨基酸、血脂等)、饮食摄入量、身体组成和总能量消耗进行纵向评估。我们的多学科团队拥有儿科营养、人类临床试验、微生物组、生物统计学的集体专业知识以及长期的合作记录，是开展这一项目的理想人选。预计这些发现将对确定促进婴儿最佳生长的饮食模式以及确定在早期补充喂养期间有利于宿主新陈代谢和生长的肠道微生物变化具有重大的科学和健康影响。这项研究的结果还将支持基于证据的婴儿饮食建议，以防止超重和后来肥胖的风险。

The overall objective of this project is to establish how infant diet with different protein-rich foods regulate growth trajectories and gut microbiota development. Both NIH and USDA are now addressing the urgent need for evidence-based dietary guidance early in life, particularly regarding protein intake, but a significant knowledge gap exists in the effects of protein-rich foods on growth and development during early complementary feeding. Early complementary feeding (~5 to 12 months of age), when infants start to consume foods beyond breastmilk or formula, is a critical transition period of developmental plasticity. Growth trajectories and shifts of the gut microbiota during this critical period have the potential to program long-term body weight, composition and disease risks and are greatly influenced by diet. Preliminary data from our pilot study in formula-fed infants demonstrated that consuming diets with two protein-rich foods: meat and dairy at a high-intake level, resulted in distinctive growth patterns from 5 to 12 months of age. An important new preliminary finding was that meat- and dairy-based foods directly affected gut microbiota diversity, composition and short-chain fatty acid production at 12 months. Changes in gut microbiota composition were also associated with infant linear growth (length gain). Here we propose three specific aims to determine how the introduction of common protein-rich foods impact infant growth (Aim 1), the development of gut microbiota (Aim 2) and the relationship between gut microbiota and infant growth (Aim 3), in a randomized controlled trial. Healthy, term infants (n=300) will be recruited and randomized to meat-, dairy-, plant-based diet groups or the reference group (standard of care), from 5 to 12 months. We will use controlled feeding (all foods provided, and formula if needed) with longitudinal assessments of gut microbiota, infant growth, blood biomarkers (IGF-1, IGFBP3, insulin, amino acids, lipids, etc.), dietary intakes, body composition, and total energy expenditure. Our multi-disciplinary team is ideally positioned to conduct this project, with collective expertise in pediatric nutrition, human clinical trials, microbiome, biostatistics, and a long-standing record of collaboration. Findings are expected to have significant scientific and health implications for determining dietary patterns that promote optimal infant growth and identifying gut microbial changes that are beneficial to the host metabolism and growth during early complementary feeding. The results of the study will also support evidence-based dietary recommendations in infants to prevent the risk of overweight and later obesity.