Structures, Functions, & Genetic Diversity of Oligosaccharides in Milk

描述(由申请人提供)：复杂的寡糖已被提出对人类健康发挥重要的生物学特性。然而，尽管简单植物低聚糖和多糖的商业化取得了进展，但这些植物代谢产物无法从根本上改变人类肠道微生物生态及其代谢，也无法改变人类的生理和疾病风险。另一方面，母乳是一种诱人的低聚糖来源，恰恰是因为母乳产生了一种独特的微生物群，这种微生物群的持久性产生了科学证明对婴儿有益的证据。母乳中的游离低聚糖是通过进化而产生的，具有惊人的丰富性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中构成了一个共生系统，刺激了共生双歧杆菌的竞争性生长。在这个项目中，我们建议建立分析、遗传和生物学工具来确定母乳中低聚糖的结构和功能，作为主题原则来指导对人类健康具有生物活性的低聚糖的开发、研究和产业化。为了实现这一目标，我们将：(A)精确地阐明整个人类乳糖的化学细节，并对不同的人类哺乳对象进行分类；(B)根据低聚糖的谱图，快速确定人类分泌者和非分泌者的状态，并将母体分泌者状态与乳寡糖组成和微生物群多样性联系起来；以及(C)利用对一系列双歧杆菌菌株的全基因组分析，建立双歧杆菌选择双歧杆菌的遗传基础。

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.