The Role of Human Milk in Infant Nutrition and Health

描述(由申请人提供)：在本次修订申请中，我们寻求对我们的项目--“母乳在婴儿营养和健康中的作用”--进行竞争性续签，该项目现已进入第31个年头。这是一项关于母乳生物活性因子的独特研究计划，解决了NICHD长期以来的一个优先事项。我们的计划项目涉及一个由高级和初级调查人员组成的高度互动的跨学科团队，他们在辛辛那提、墨西哥和波士顿拥有核心和项目。母乳喂养传达了保护儿童健康的强大生物活性因素。在当前的赠款周期中，我们已经证明，母乳中的多糖，特别是A1，2岩藻糖基(“分泌物”)低聚糖及其高分子量糖偶联物，是一类主要的新型抗菌剂。我们已经在生物工程菌中初步合成了人乳汁分泌物低聚糖类似物(H-2 on LNneT)。在这次竞争更新中，我们将重点放在具有三大功能-病原体结合抑制、益生菌活性和抗炎活性的新型抗菌剂上，以保护母乳喂养的儿童免受肠道感染和炎症性疾病的侵袭，提出了三个与人乳多糖有关的项目：1)抑制细菌性胃肠炎；2)抑制病毒性胃肠炎；以及3)调节炎症、定植和粘膜发育。在每个项目中，我们都提出了基础、临床和转化性研究。将进行两条互补的翻译研究路线：1)开发和测试作为新型抗菌剂的人奶多糖类似物，以及2)测试分泌物表型作为肠道感染和炎症性疾病的新型临床生物标记物。这些项目将得到生物统计学(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路线图2008年与炎症、微生物组和表型相关的优先事项。

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.