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

项目总结/摘要 这是一个修改后的竞争性更新，继续在我们的母婴西班牙裔二人组的出生队列工作。通过 对母乳进行重复采样和分析，沿着婴儿从出生到 2 y的年龄，我们已经在母婴营养领域做出了重大贡献。这项工作扩展了我们的 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、饮食行为和认知发育的影响。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）。目标1将研究婴儿接触 母乳喂养期间的HMO对肥胖和食欲调节的影响，重点关注5个HMO， 与既往/正在进行的研究存在显著关联。我们假设这些HMO将与 减少肥胖（皮下，内脏和肝脏脂肪），这将通过减少饮食来介导。 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 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MRI）、功能（静息状态fMRI）、血流（动脉自旋标记）和髓鞘形成， 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），将与改善的大脑结果相关。 这将包括：a）皮质覆盖层变厚，皮质灰质内各向异性分数降低 （代表更大的树突分支）; B）皮质灰质的静息灌注减少（代表 更大的神经元代谢效率）; c）白色物质束中的扩散率降低（代表更多 髓鞘形成）; d）静息功能连接的更强测量（代表更有效的信息 转移），和e）增强的认知结果。目标3将研究母乳喂养对饮食的影响， 没有饥饿感，大脑中与食欲有关的关键区域存在结构和功能差异 调控我们假设，母乳喂养时间越长，接触3FL的机会越大， 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 皮质套和减少与食欲调节相关的脑区的分数各向异性。本研究 将通过确定早期生活饮食暴露（母乳喂养，HMO和HMO）如何推动该领域的发展 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， 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.