Role of Human Milk Oligosaccharides on Infant Brain Development

项目摘要 优化早期认知发展至关重要，因为认知受损的儿童面临更大的风险， 神经精神疾病虽然众所周知，母乳喂养促进更好的认知 然而，在母乳的发育过程中，很少有研究确定母乳中参与这一过程的特定成分。 一个可能相关的成分是一组不可消化的复合碳水化合物，称为人类碳水化合物。 乳低聚糖（HMO）。动物研究表明，某些HMO可以增强 记忆、注意力和冲动控制，并且这种关系可能由几种机制驱动。第一、 一些HMO是大脑发育重要唾液酸的来源。第二，HMO是一个来源， 益生元对肠道微生物的发育很重要，这可能在认知发育中发挥作用， 父R01的焦点。虽然生命的第一年是大脑发育的关键窗口期， HMO是否影响婴儿认知的结构功能组织。在这个应用程序中，佩奇博士 Berger的目标是确定HMO和磁共振成像（MRI）测量之间的关联 婴儿大脑发育（大脑白色物质髓鞘形成，皮质成熟）。在K99阶段，她 将建立在现有的NIH申办的研究（R01DK110793）由迈克尔·戈兰博士。在父R01中， 西班牙裔母亲和正常出生体重的婴儿正在接受随访，经常评估HMO， 24个月在拟议的项目中，Berger博士将利用健康维护组织的数据和资源， 1个月和6个月时纯母乳喂养的母婴对（n=65）。由于脑白色物质髓鞘形成 和皮质成熟没有在父母R01中测量，Berger博士将在1岁和6岁的婴儿中收集这些数据。 个月K99假说认为，在正常出生体重婴儿（≥2500 g）中，脑白色物质髓鞘形成 皮质成熟与HMO呈正相关。Berger博士将把她的K99培训集中在 发展婴儿认知的结构功能组织方面的专业知识，并磨练她在以下方面的技能： 开展母婴临床营养研究。她将学习所需的技能和技巧， 在她的专家团队（Goran、布拉德利彼得森、Lars Bode、Leann Birch，道格拉斯范德比尔特）。总的来说，她的专家团队在培养博士后方面有着良好的记录 学者们正在走向独立。在R00阶段，Berger博士将应用在 指导阶段，在低出生体重婴儿（<2500 g）中开展新的工作，检查 健康维护组织和认知发展之间的关系拟议的工作将为伯杰博士提供数据和支持 开发高效和有效的临床试验，未来的影响，以验证HMO的作用， 对高危婴儿群体的认知发育有积极影响。

PROJECT SUMMARY Optimizing early cognitive development is critical, as children with impaired cognition are at greater risk for neuropsychiatric disorders later in life. While it is known that breastfeeding promotes better cognitive development, few studies have identified specific components of breast milk that are involved in this process. One component that may be relevant is a group of non-digestible complex carbohydrates known as human milk oligosaccharides (HMOs). Animal studies reveal that certain HMOs enhance cognitive outcomes of memory, attention, and impulse control, and the relationship may be driven by several mechanisms. First, some HMOs are a source of sialic acid important for brain development. Second, HMOs are a source of prebiotics important for gut microbe development, which is likely to play a role in cognitive development and a focus of the parent R01. Although the first year of life is a critical window for brain development, it is unknown whether HMOs affect structural-functional organization of infant cognition. In this application, Dr. Paige Berger’s goal is to determine associations between HMOs and magnetic resonance imaging (MRI) measures of infant brain development (brain white matter myelination, cortical maturation). During the K99 phase, she will build on an existing NIH sponsored study (R01DK110793) by Dr. Michael Goran. In the parent R01, Hispanic mothers and normal birth weight infants are being followed, with frequent assessment of HMOs up to 24 months. In the proposed project, Dr. Berger will leverage the data and resources on HMOs in a subset of exclusively breastfeeding mother-infant pairs (n=65) at 1 and 6 months. Since brain white matter myelination and cortical maturation were not measured in the parent R01, Dr. Berger will collect these in infants at 1 and 6 months. The K99 hypothesis is that in normal birth weight infants (≥2500 g), brain white matter myelination and cortical maturation will be positively associated with HMOs. Dr. Berger will focus her K99 training on the development of expertise in structural-functional organization of infant cognition, and hone her skills in conducting clinical nutrition research in mother-infant pairs. She will learn the skills and techniques needed to complete the proposed research under her expert team (Drs. Goran, Bradley Peterson, Lars Bode, Leann Birch, Douglas Vanderbilt). Collectively, her expert team has a strong track record of training postdoctoral scholars transitioning to independence. In the R00 phase, Dr. Berger will apply the skills acquired during the mentored phase to initiate a new line of work in low birth weight infants (<2500 g), examining associations between HMOs and cognitive development. The proposed work will provide Dr. Berger with data and support to develop efficient and effective clinical trials, with future implications to validate the roles of HMOs that may have positive effects on cognitive development in a high-risk infant population.