Structures, Functions, & Genetic Diversity of Oligosaccharides in Milk

结构、功能、

• 批准号: 8096559
• 负责人: CARLITO B LEBRILLA
• 金额: $ 32.4万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8096559
• 关键词: Bacteria; Bacterial Genome; Behavior; Bifidobacterium; Binding; Binding Proteins; Biological; Biological Assay; Breast Feeding; Catabolism; Cell surface; Chemicals; Complex; Consumption; Ecology; Enzymes; Evolution; Food; Fucosidase; Gene Proteins; Genetic; Genetic Variation; Genome; Genomics; Goals; Growth; Health; High Pressure Liquid Chromatography; Human; Human Milk; Individual; Industrialization; Infant; Laboratories; Lactose; Link; Metabolism; Methods; Microbiology; Milk; Mothers; Nutritional; Oligosaccharides; Phenotype; Physiology; Plants; Polysaccharides; Principal Investigator; Property; Relative (related person); Research; Research Personnel; Sequence Analysis; Source; Specificity; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Structure; Surface; System; Work; analytical tool; base; commercialization; comparative genomics; disorder risk; food science; genome sequencing; microbial; offspring; prebiotics; programs; rapid technique; research and development; sugar; tool

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.

描述（由申请人提供）：复合寡糖已被提议对人类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无法显着改变人类肠道微生物生态及其代谢，也无法显着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，正是因为母乳产生了独特的微生物群，其持久性提供了科学证据证明对人类婴儿有益。母乳中的游离寡糖通过进化而出现，数量非常丰富，并且具有显着的结构多样性。合作实验室的研究表明，这些寡糖在人类婴儿中构成了一个共生系统，刺激共生双歧杆菌的竞争性生长。在该项目中，我们建议建立分析、遗传和生物学工具来建立母乳中低聚糖的结构和功能，作为指导用于人类健康的生物活性低聚糖的开发、研究和产业化的主题原则。为了实现这一目标，我们将：（A）以精确的化学细节阐明整个母乳糖组，并对不同表达寡糖组成的不同人类哺乳期受试者进行分类，（B）开发分析工具来快速确定人类分泌者与基于寡糖谱的非分泌者状态，并将母体分泌者状态与乳汁寡糖组成和微生物群多样性联系起来，以及（C）通过人乳整体中的特定结构建立双歧杆菌选择的遗传基础使用一系列双歧杆菌菌株的全基因组分析，将细菌消耗的特定寡糖与细菌表面内和表面的基因和蛋白质的功能分析联系起来。