Structures, Functions, & Genetic Diversity of Oligosaccharides in Milk

描述（由申请人提供）：已提出复合寡糖对人类健康发挥重要的生物学特性。然而，尽管简单的植物寡糖和多糖的商业化取得了进展，但这些植物代谢产物不能实质性改变人类肠道微生物生态，也不能改变其代谢，也不能改变人类的生理学和疾病风险。另一方面，人乳是一种有吸引力的低聚糖来源，正是因为人乳产生独特的微生物群，其持久性产生了科学确定的证据，证明对人类婴儿有益。人乳中的游离低聚糖通过进化以显著的丰度和显著的结构多样性出现。合作实验室的研究表明，这些低聚糖在人类婴儿体内构成了一个共生系统，刺激了肠道细菌的竞争性生长。在本项目中，我们建议建立分析，遗传和生物学工具，以建立人乳中低聚糖的结构和功能作为主题原则，以指导开发，研究和产业化的生物活性低聚糖对人类健康。为了实现这一目标，我们将：（A）以精确的化学细节阐明整个人乳糖组，并对在表达的寡糖组成方面不同的人类哺乳受试者的多样性库进行分类，（B）开发分析工具以基于寡糖谱快速确定人类分泌型与非分泌型状态，并将母体分泌型状态与乳寡糖组成和微生物群多样性联系起来，和（C）使用一系列双歧杆菌菌株的全基因组分析，通过人乳寡糖总体中的特定结构建立双歧杆菌选择的遗传基础，将细菌的特定寡糖消耗与细菌表面内和表面上的基因和蛋白质的功能分析相关联。

DESCRIPTION (provided by applicant): Complex oligosaccharides have been proposed to exert important biological properties for human health. However, despite advances in the commercialization of simple plant oligosaccharides and polysaccharides, these products of plant metabolism are unable to substantially alter the human gut microbial ecology nor its metabolism nor the physiology and disease risks of humans. Human milk, on the other hand, is an attractive source of oligosaccharides precisely because human milk produces a unique microbiota whose persistence yields scientifically established evidence of benefits to human infants. The free oligosaccharides in human milk have emerged through evolution in remarkable abundance and with significant structural diversity. Research in the collaborating laboratories has demonstrated that these oligosaccharides constitute a symbiotic system in human infants stimulating the competitive growth of commensal bifidobacteria. In this project we propose to build the analytic, genetic and biological tools to establish the structures and functions of the oligosaccharides in human milk as thematic principles to guide the development, research and industrialization of bioactive oligosaccharides for human health. To achieve this goal, we will: (A) elucidate in precise chemical detail the entire human milk glycome and categorize a diverse pool of human lactating subjects differing in the composition of expressed oligosaccharides, (B) develop analytical tools to rapidly determine human secretor versus non- secretor status based on the oligosaccharide profile and link maternal secretor status to milk oligosaccharide composition and microbiota diversity, and (C) establish the genetic basis of bifidobacterial selection by the specific structures in the ensemble of human milk oligosaccharides using whole genomic analysis of a range of bifidobacterial strains, relating specific oligosaccharide consumption by bacteria to functional analysis of genes and proteins in and on bacterial surfaces.