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

项目摘要/摘要 这是一个修改后的竞争性更新，以继续在我们出生的拉美裔母亲-婴儿二元组中工作。穿过 对母乳进行反复抽样和分析，并对婴儿从出生到出生进行详细和反复的评估 2岁时，我们在母婴营养领域做出了重大贡献。这项工作扩展了我们的 人乳低聚糖(HMOS)的作用及其在妊娠过程中的动态变化 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，重点检查医疗保健组织在以下方面的作用 肥胖症(腹部核磁共振)、食欲调节(不饥饿时吃饭)、大脑结构和功能 (多模式磁共振成像)和认知结果(NIH工具箱)。目标1将研究婴儿暴露于 HMO在母乳喂养期间对肥胖和食欲调节的作用，重点介绍了已证明的5种HMO 先前/正在进行的研究中的重大关联。我们假设这些医疗保健组织将与 减少肥胖(皮下、内脏和肝脏脂肪)，这将通过减少饮食在 没有饥饿。目标2将研究婴儿暴露于提供岩藻糖来源的HMO的影响 唾液酸对大脑发育很重要。我们将使用多模式磁共振成像来评估大脑 结构(解剖MRI)、功能(静息状态fMRI)、血流(动脉自旋标记)、髓鞘形成和 组织微结构(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，2‘FL，并继续暴露于3FL和3’SL(唯一的 我们发现在母乳喂养期间增加的HMO)，将与改善大脑结果有关。 这将包括：a)皮质地幔更厚，皮质灰质内的各向异性分数减少 (代表更大的树突分支)；b)皮质灰质静息灌注量减少(代表 更高的神经元代谢效率)；c)白质束弥散系数降低(代表 髓鞘形成)；d)更强的静息功能连通性测量(代表更有效的信息 转移)，以及e)增强认知结果。目标3将研究母乳喂养对儿童饮食的影响。 没有饥饿以及与食欲有关的大脑关键区域的结构和功能差异 监管。我们假设，较长时间的母乳喂养，因此更多地暴露在3FL和 在没有饥饿的情况下，3‘SL将与进食量减少相关，这将通过更厚的 与食欲调节相关的大脑区域的皮质外套膜和减少的部分静止。本研究 将通过确定早期饮食暴露(母乳喂养、HMO和HMO)将推动这一领域向前发展 母乳喂养过程中的变化)影响肥胖、食欲调节、大脑结构和功能以及 儿童早期发展的认知结果。

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.