Role of Human Milk Oligosaccharides on Brain Development in Preterm Infants

母乳低聚糖对早产儿大脑发育的作用

• 批准号: 10580137
• 负责人: Paige Kimberly Berger
• 金额: $ 24.92万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10580137
• 关键词: Adult; Affect; Anatomy; Animals; Area; Attention; Betula Genus; Birth Weight; Body Composition; Brain; Brain Injuries; Breast Feeding; Breastfed infant; California; Carbohydrates; Child; Clinical Nutrition; Clinical Trials; Cognition; Cognitive deficits; Complex; Data; Development; Diffusion Magnetic Resonance Imaging; Exclusive Breastfeeding; Exposure to; Feasibility Studies; Fostering; Foundations; Funding; Future; Goals; Hispanic; Human Milk; Impaired cognition; Infant; Inflammation; Lead; Learning Skill; Life; Los Angeles; Low Birth Weight Infant; MRI Scans; Magnetic Resonance Imaging; Measures; Memory; Mentors; Mothers; Nutritional; Nutritional Study; Oligosaccharides; Outcome; Outcome Measure; Parents; Pediatric Hospitals; Phase; Play; Population; Premature Infant; Process; Research; Resources; Risk; Role; Shapes; Sialic Acids; Signal Transduction; Source; Structure; Techniques; Training; United States National Institutes of Health; Universities; Work; brain magnetic resonance imaging; career; cognitive development; cognitive enhancement; data resource; dietary; feeding; gray matter; gut dysbiosis; gut inflammation; gut microbes; gut microbiome; high risk infant; high risk population; myelination; neuropsychiatric disorder; post-doctoral training; prebiotics; recruit; skills; white matter

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.

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着更大的风险 神经精神疾病后期。虽然众所周知，母乳喂养会促进更好的认知 开发，很少有研究确定了这一过程中涉及的母乳的特定组成部分。 可能相关的一种组成部分是一组不可消化的复合碳氢化物，称为人类 牛奶寡糖（HMOS）。动物研究表明，某些HMO增强了认知结果 记忆，注意力和冲动控制，并且关系可以由多种机制驱动。第一的， 一些HMO是唾液酸对脑发育重要的来源。其次，HMOS是 益生元对于肠道微生物发育很重要，这可能在认知发展中发挥作用 父母R01的焦点。尽管生命的第一年是大脑发育的关键窗口，但尚不清楚 HMO是否影响婴儿认知的结构性功能组织。在此申请中，Paige博士 Berger的目标是确定HMOS与磁共振成像（MRI）测量之间的关联 婴儿脑发育（脑白质髓鞘，皮质成熟）。在K99阶段，她 将基于Michael Goran博士的现有NIH赞助研究（R01DK110793）。在父r01中 遵循西班牙裔母亲和正常的出生体重婴儿，经常评估HMO 24个月。在拟议的项目中，Berger博士将在一部分中利用HMO的数据和资源 在1个月和6个月时，专门母乳喂养的母乳喂养（n = 65）。由于脑白质髓囊 在父r01中未测量皮质成熟，Berger博士将在1和6的婴儿中收集它们 月份。 K99假设是在正常出生体重婴儿（≥2500g）中，脑白质髓鞘化 皮质成熟将与HMO呈正相关。 Berger博士将把她的K99培训集中在 发展婴儿认知组织结构功能组织的专业知识，并磨练她的技能 在母亲对进行临床营养研究。她将学习所需的技能和技巧 完成她的专家团队的拟议研究（Goran博士，Bradley Peterson，Lars Bode，Leann 桦木，道格拉斯·范德比尔特）。总的来说，她的专家团队在训练博士后方面有着良好的记录 学者过渡到独立。在R00阶段，Berger博士将应用在此期间获得的技能 指导阶段以低出生体重婴儿（<2500 g）的新作品开始工作，检查关联 在HMO和认知发展之间。拟议的工作将为Berger博士提供数据和支持 为了开发有效有效的临床试验，未来的影响是验证HMO的作用 对高危婴儿人群的认知发展有积极影响。