Structures, Functions, & Genetic Diversity of Oligosaccharides in Milk

描述（由申请人提供）：复合寡糖已被提出对人体健康发挥重要的生物学特性。然而，尽管简单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地改变人类肠道微生物生态及其代谢，也不能改变人类的生理和疾病风险。另一方面，母乳是一种有吸引力的低聚糖来源，正是因为母乳产生一种独特的微生物群，这种微生物群的持久性产生了对人类婴儿有益的科学证据。人乳中的游离寡糖是经过进化而产生的，具有显著的丰度和显著的结构多样性。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，刺激共生双歧杆菌的竞争性生长。本项目拟建立分析、遗传和生物学工具，以确定母乳中低聚糖的结构和功能，并以此为主题原则，指导对人类健康有益的生物活性低聚糖的开发、研究和产业化。为实现这一目标，我们将：(A)阐明整个人乳糖的精确化学细节，并对不同表达寡糖组成的不同人类泌乳受试者进行分类；(B)开发分析工具，根据寡糖谱快速确定人类分泌和非分泌状态，并将母体分泌状态与牛奶寡糖组成和微生物群多样性联系起来。(C)利用一系列双歧杆菌菌株的全基因组分析，通过人乳低聚糖集合中的特定结构建立双歧杆菌选择的遗传基础，将细菌对特定低聚糖的消耗与细菌表面和细菌表面的基因和蛋白质的功能分析联系起来。

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.