The Role of Human Milk in Infant Nutrition and Health

描述（由申请人提供）：在此修订后的申请中，我们寻求我们的计划项目“母乳在婴儿营养和健康中的作用”的竞争性更新，该项目现已进入第31个年头。这是一个关于母乳生物活性因子的独特研究项目，解决了NICHD长期以来的优先事项。我们的计划项目涉及一个高度互动的，跨学科的高级和初级研究人员团队，在辛辛那提，墨西哥和波士顿的核心和项目。母乳喂养传递了保护儿童健康的有效生物活性因子。在当前的资助周期中，我们已经证明人乳聚糖，特别是α 1，2岩藻糖基（“分泌型”）寡糖及其高分子量糖缀合物，是一类主要的新型抗菌剂。我们已经在生物工程菌中实现了人乳分泌寡糖类似物（LNneoT上的H- 2）的初步合成。在这次竞争性更新中，我们重点关注人乳聚糖作为新型抗菌剂，具有三种主要功能-病原体结合抑制，益生元活性和抗微生物活性-保护母乳喂养的儿童免受肠道传染病和炎症性疾病的侵害，提出了三个与人乳聚糖有关的项目：1）抑制细菌性胃肠炎; 2）抑制病毒性胃肠炎;和3）炎症、定殖和粘膜发育的调节。在每个项目中，我们提出基础，临床和转化研究。将进行两条互补的转化研究路线：1）开发和测试人乳聚糖类似物作为新型抗菌剂，2）测试分泌表型作为肠道感染性和炎症性疾病的新型临床生物标志物。这些项目将得到生物计量学（流行病学，生物统计学和信息学），糖生物学和分子生物学核心的支持。我们的重点和方法解决了NIH 2008年路线图关于炎症，微生物组和表型的优先事项。 公共卫生相关性：本申请中提出的研究旨在改变我们对母乳聚糖和婴儿聚糖与疾病风险相关的基本理解，并将我们的发现转化为改善婴儿和儿童健康的新疗法，饮食干预和诊断工具。

DESCRIPTION (provided by applicant): In this revised application, we seek competitive renewal of our program project, "The Role of Human Milk in Infant Nutrition and Health," which is now entering its 31st year. This is a unique research program on human milk bioactive factors that addresses a long-standing priority of NICHD. Our program project involves a highly interactive, interdisciplinary team of senior and junior investigators with cores and projects at Cincinnati, Mexico, and Boston. Breastfeeding conveys potent bioactive factors that protect child health. During the current grant cycle we have shown that the human milk glycans, particularly, the a1,2 fucosyl ("secretor") oligosaccharides and their high molecular weight glycoconjugates, are a major new class of antimicrobial agents. We have achieved initial synthesis of human milk secretor oligosaccharide analogs (H- 2 on LNneoT) in bioengineered bacteria. In this competitive renewal, we focus on the human milk glycans as novel antimicrobials with three major functions - pathogen-binding inhibition, prebiotic activity, and antiinflammatory activity - that protect breastfeeding children against enteric infectious and inflammatory diseases, three projects are proposed pertaining to the human milk glycans: 1) Inhibition of bacterial gastroenteritis; 2) Inhibition of viral gastroenteritis; and 3) Modulation of inflammation, colonization, and mucosal development. In each project, we propose basic, clinical and translational research. Two complementary lines of translational research will be pursued: 1) Developing and testing human milk glycan analogs as novel antimicrobials and 2) testing the secretor phenotype as a novel clinical biomarker for enteric infectious and inflammatory diseases. The projects will be supported by cores in Biometry (Epidemiology, Biostatistics, and Informatics); Glycobiology; and Molecular Biology. Our focus and approach addresses NIH Road Map 2008 priorities pertaining to inflammation, the microbiome, and phenotyping. PUBLIC HEALTH RELEVANCE: The research proposed in this application is designed to transform our fundamental understanding of human milk glycans and infant glycans in relation to disease risk and translate our discoveries into novel therapeutics, dietary interventions, and diagnostic tools that improve infant and child health.