"Impact of Early feeding and human milk oligosaccharides on obesity and brain development".

“早期喂养和母乳低聚糖对肥胖和大脑发育的影响”。

• 批准号: 10669747
• 负责人: Michael Isaac Goran
• 金额: $ 69.55万
• 依托单位: CHILDREN'S HOSPITAL OF LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-07 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669747
• 关键词: Abdomen; Affect; Age; Age Months; Anatomy; Anisotropy; Appetite Regulation; Area; Basal Ganglia; Birth; Blood flow; Body fat; Body measure procedure; Brain; Brain imaging; Brain region; Breast; Breast Feeding; Breastfed infant; Carbohydrates; Cognitive; Complex; Data; Development; Diffusion Magnetic Resonance Imaging; Dual-Energy X-Ray Absorptiometry; Early identification; Eating; Eating Behavior; Ethics; Exposure to; Fatty acid glycerol esters; Fucose; Functional Magnetic Resonance Imaging; Growth; Growth and Development function; Hippocampus; Hispanic; Human Milk; Hypothalamic structure; Image; Infant; Infant Food; Infant formula; Knowledge; Laboratories; Language; Life; Link; Liver; Logistics; Magnetic Resonance; Magnetic Resonance Imaging; Measures; Mediating; Metabolic; Methods; Mothers; Motor; Neurons; Obesity; Oligosaccharides; Outcome; Perfusion; Play; Population; Questionnaires; Radiation; Rest; Role; Sampling; Series; Sialic Acids; Source; Structure; Thinness; Time; Tissues; Toddler; United States National Institutes of Health; Visceral; Weight Gain; Work; arterial spin labeling; brain magnetic resonance imaging; cognitive development; cognitive enhancement; cognitive function; cognitive performance; cognitive testing; cohort; design; dietary; early childhood; eating in absence of hunger; feeding; follow-up; frontal lobe; gray matter; gut microbiome; immune function; improved; infant adiposity; infant nutrition; infant outcome; multimodality; myelination; novel; prebiotics; reduced food intake; subcutaneous; white matter

Project Summary/Abstract This is a revised competing renewal to continue work in our birth cohort of mother-infant Hispanic dyads. Through repeated sampling and analysis of breastmilk, along with detailed and repeated infant assessments from birth to 2y of age, we have made significant contributions to the field of maternal-infant nutrition. This work extended our knowledge on the role of human milk oligosaccharides (HMOs), and their dynamic changes during the course of breastfeeding, on infant growth, obesity, eating behaviors, and cognitive development. Based on novel findings, we propose a series of new rigorous assessments at age 5y, with a focus on examining the role of HMOs on adiposity (abdominal MRI), appetite regulation (eating in the absence of hunger), brain structure and function (multimodal MRI), and cognitive outcomes (NIH toolbox). Aim 1 will examine the impact of infant exposure to HMOs during breastfeeding on obesity and appetite regulation, with a focus on 5 HMO’s that have demonstrated significant associations in prior/ongoing studies. We hypothesize that these HMOs will be associated with reduced adiposity (subcutaneous, visceral, and liver fat), and this will be mediated by reduced eating in the absence of hunger. Aim 2 will examine the impact of infant exposure to HMOs that provide a source of fucose and sialic acid that are important for brain development. We will use multimodal MRI for assessment of brain structure (anatomical MRI), function (resting state fMRI), blood flow (arterial spin labeling), and myelination and tissue microstructure (diffusion tensor imaging) as well as cognitive outcomes. Based on preliminary data, we hypothesize that 2’FL during the first month of breastfeeding, and continued exposure to 3FL and 3’SL (the only HMOs which we have found to increase during breastfeeding), will be associated with improved brain outcomes. This will include: a) thicker cortical mantle and reduced fractional anisotropy within cortical gray matter (representing greater dendritic arborization); b) reduced resting perfusion of cortical gray matter (representing greater neuronal metabolic efficiency); c) reduced diffusivity in white matter tracts (representing more myelination); d) stronger measures of resting functional connectivity (representing more efficient information transfer), and e) enhanced cognitive outcomes. Aim 3 will examine the impact of breast feeding on eating in the absence of hunger and structural and functional differences in key areas of the brain involved with appetite regulation. We hypothesize that longer-term duration breastfeeding, and therefore greater exposure to 3FL and 3’SL, will be associated with reduced eating in the absence of hunger, and this will be mediated by a thicker cortical mantle and reduced fractional anistrophy in brain regions associated with appetite regulation. This study will move the field forward by identifying how early-life dietary exposures (breastfeeding, HMOs and HMO changes during the course of breastfeeding) affect obesity, appetite regulation, brain structure and function and cognitive outcomes during early childhood development.

项目概要/摘要 这是一项经过修订的竞争性更新，旨在继续在我们的西班牙裔母婴出生队列中开展工作。 对母乳进行重复采样和分析，以及从出生到婴儿的详细和重复评估 2岁的时候，我们就在母婴营养领域做出了重大贡献。这项工作扩展了我们的视野。 了解母乳低聚糖（HMO）的作用及其在母乳喂养过程中的动态变化 母乳喂养对婴儿生长、肥胖、饮食行为和认知发展的影响基于新的发现， 我们建议在 5 岁时进行一系列新的严格评估，重点是检查 HMO 在以下方面的作用： 肥胖（腹部 MRI）、食欲调节（在没有饥饿的情况下进食）、大脑结构和功能 （多模态 MRI）和认知结果（NIH 工具箱）将检查婴儿暴露的影响。 母乳喂养期间的 HMO 对肥胖和食欲调节的影响，重点关注 5 种已被证实的 HMO 我们发现这些 HMO 与之前/正在进行的研究存在显着关联。 减少肥胖（皮下脂肪、内脏脂肪和肝脏脂肪），这将通过减少体内饮食来介导 目标 2 将检查婴儿接触提供岩藻糖来源的 HMO 的影响。 我们将使用多模态 MRI 来评估大脑。 结构（解剖 MRI）、功能（静息态 fMRI）、血流（动脉自旋标记）和髓鞘形成 组织微观结构（扩散张量成像）以及认知结果根据初步数据，我们。 在母乳喂养的第一个月期间保持 2'FL，并继续暴露于 3FL 和 3'SL（唯一的 我们发现 HMO 在母乳喂养期间会增加），这与改善大脑结果有关。 这将包括：a）更厚的皮质地幔和减少皮质灰质内的分数各向异性 （代表更大的树突状树枝化）；b）皮质灰质的静息灌注减少（代表 c）白质束的扩散率降低（代表更多 髓鞘形成）；d）更强的静息功能连接测量（代表更有效的信息） e) 增强认知结果 目标 3 将检查母乳喂养对饮食的影响。 缺乏饥饿感以及与食欲有关的大脑关键区域的结构和功能差异 我们追求更长期的母乳喂养，因此更多地接触 3FL 和 3'SL，将与在没有饥饿的情况下减少进食有关，这将通过较厚的 这项研究显示，大脑皮层套和与食欲调节相关的大脑区域的分数各向异性减少。 将通过确定生命早期饮食暴露（母乳喂养、HMO 和 母乳喂养过程中的变化）影响肥胖、食欲调节、大脑结构和功能， 儿童早期发展期间的认知结果。