"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: 10367893
• 负责人: Michael Isaac Goran
• 金额: $ 75.01万
• 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/10367893
• 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; Diffuse; Diffusion Magnetic Resonance Imaging; Dual-Energy X-Ray Absorptiometry; Eating; Eating Behavior; Ethics; Exposure to; Fatty acid glycerol esters; Fucose; Functional Magnetic Resonance Imaging; Growth; Growth and Development function; Hippocampus (Brain); Hispanics; 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; Spin Labels; Structure; Thick; Thinness; Time; Tissues; Toddler; United States National Institutes of Health; Visceral; Weight Gain; Work; base; 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.

项目摘要/摘要 这是一个经过修订的竞争续约，以继续在我们的母亲西班牙裔二元组的诞生中工作。通过 对母乳的重复采样和分析，以及从出生到的详细和重复的婴儿评估 2岁时，我们为产妇营养领域做出了重大贡献。这项工作扩大了我们的 了解人牛奶寡糖（HMO）的作用及其在过程中的动态变化 母乳喂养，婴儿生长，肥胖，饮食行为和认知发展。基于新颖的发现 我们在5岁时提出了一系列新的严格评估，重点是研究HMO在 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 （多模式MRI）和认知结果（NIH工具箱）。 AIM 1将检查婴儿接触的影响 HMO在肥胖和食欲调节的母乳喂养期间，重点是5 HMO 在先验/正在进行的研究中的重要关联。我们假设这些HMO将与 脂肪降低（皮下，内脏和肝脏脂肪），这将通过减少饮食来介导 缺乏饥饿。 AIM 2将检查婴儿暴露于HMO的影响，该HMO提供了岩藻糖的来源 和唾液酸对大脑发育很重要。我们将使用多模式MRI评估大脑 结构（解剖学MRI），功能（静止状态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 假设在母乳喂养的第一个月中，2’Fl，并继续暴露于3FL和3’SL（唯一） 我们发现在母乳喂养期间增加的HMO将与改善大脑结局有关。 这将包括：a）皮质灰质内较厚的皮质地幔和降低的分数各向异性 （代表更大的树突状树木化）； b）减少皮质灰质的静息灌注（代表 更大的神经元代谢效率）； c）降低白质区域的扩散率（代表更多 髓鞘）； d）静止功能连接性的强有力衡量（代表更有效的信息 转移）和e）增强的认知结果。 AIM 3将检查母乳喂养对进食的影响 与食欲有关 规定。我们假设长期持续时间母乳喂养，因此更大的3FL暴露 3'sl，将在没有饥饿的情况下减少饮食，这将由较厚的 与食欲调节相关的大脑区域的皮质地幔和降低的分数。这项研究 通过确定早期饮食的暴露方式（母乳喂养，HMOS和HMOS），将向前进。 母乳喂养过程中的变化）会影响肥胖，食欲调节，大脑结构和功能以及 幼儿发展期间的认知结果。