The Role of Human Milk in Infant Nutrition and Health

描述（由申请人提供）：在这份修订后的申请中，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。我们的项目包括一个高度互动的跨学科团队，由辛辛那提、墨西哥和波士顿的高级和初级研究人员组成。母乳喂养具有保护儿童健康的强有力的生物活性因素。在当前的资助周期中，我们已经表明，人乳聚糖，特别是a1,2焦酰基（“分泌”）寡糖及其高分子量糖缀合物，是一类重要的新型抗菌剂。我们已经在生物工程细菌中初步合成了人乳分泌物低聚糖类似物（LNneoT上的H- 2）。在这一竞争更新中，我们将重点关注人乳聚糖作为具有病原体结合抑制、益生元活性和抗炎活性的新型抗菌剂，以保护母乳喂养的儿童免受肠道感染性和炎症性疾病的侵害，并提出了三个与人乳聚糖相关的项目：1)抑制细菌性胃肠炎；2)抑制病毒性肠胃炎；3)炎症、定植和粘膜发育的调节。在每个项目中，我们提出基础研究、临床研究和转化研究。两个互补的转化研究方向将继续进行：1)开发和测试人乳聚糖类似物作为新型抗菌剂；2)测试作为肠道感染性和炎症性疾病的新型临床生物标志物的分泌表型。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）核心的支持；糖生物学;分子生物学。我们的重点和方法解决NIH路线图2008年有关炎症，微生物组和表型的优先事项。

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.