Activation of probiotic bifidobacteria by milk glyans

乳聚糖激活益生菌双歧杆菌

• 批准号: 8914110
• 负责人: Bruce German
• 金额: $ 85.64万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2019-08-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914110
• 关键词: Address; Adherence; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Autonomic nervous system; Bacteria; Bifidobacterium; Biological; Breast Feeding; Catabolism; Cattle; Chronic; Complex; Consumption; Data; Development; Diagnostic; Diet; Disease; Enteroendocrine Cell; Environment; Epithelial; Epithelial Cells; Epithelium; Fatty acid glycerol esters; Gastrointestinal tract structure; Glycoconjugates; Glycoproteins; Goals; Growth; Health; Homeostasis; Human; Human Milk; Hydrolase; Immune response; Immune system; In Vitro; Infant; Inflammation; Inflammation Mediators; Ingestion; Intervention; Intestinal Diseases; Intestines; Inulin; Knowledge; Lactation; Large Intestine; Lead; Link; Mammals; Maps; Measurement; Mediator of activation protein; Metabolic Diseases; Milk; Mission; Modification; Nervous System Physiology; Oligosaccharides; Outcome; Outcome Measure; Pathologic Processes; Pathway interactions; Phenotype; Polysaccharides; Principal Investigator; Probiotics; Process; Production; Rattus; Research; Rodent; Rodent Model; Series; Small Intestines; Societies; Stream; Testing; Tissues; Translating; Work; base; brain pathway; design; early childhood; effective therapy; gut microbiota; improved; in vivo; infancy; inflammatory marker; insight; intestinal epithelium; metabolomics; metagenome; microbiome; prebiotics; programs; repaired; response; sugar; tool; transcriptomics

Program Director/Principal Investigator (Last, First, Middle): MIIIS, D a v l d , A . PROJECT SUMMARY (See instmctions): The use of prebiotics and probiotics to restore a healthy gut microbiota represent a desirable target, but the lack of mechanistically relevant signatures of how specific bacteria interact with the intestinal environment and the host has hindered the development of effective and well-characterized prebiotic and probiotic treatments. The long-term goal is to translate the successful strategy of mammalian lactation, shown using human milk glycans, to the development of targeted, effective synbiotics by using plentiful and available bovine milk glycan streams. The overarching hypothesis to be tested is that the evolutionary relationship between infant-borne bifidobacteria and bovine milk glycans and glycoconjugates produce a synergistic human milk glycan-like phenotype that can effectively colonize, restore a healthy gut microbiota and induce host response to better protect epithelial barrier function and thus improve health outcomes. First, the team will address whether in infant-borne bifidobacteria species, complex milk glycoconjugates induce specific glycosyl hydrolases and transporters that are necessary to consume these complex substrates. Milk glycoconjugate catabolism by infant-borne bifidobacteria will be examined by detailed transcriptomics, specific enzymatic and transporter analysis, and glycoprofiling to identify precise links between glycan components and their cognate bifidobacterial processing mechanisms. Second, the research team will determine whether select infant-borne bifidobacteria that consume complex milk glycoconjugates compared to simple sugar substrates are more effective in inducing a protective response within the host epithelium. Measurements of bifidobacterial adherence, improved barrier function, release of inflammatory mediators and activation of enteroendocrine cells will be obtained from gut epithelial and enteroendocrine cells in vitro and ex vivo in rat small and large intestinal tissue. Finally, the team will determine whether modulation of intestinal function by application of synbiotic milk glycan- and glycoconjugate-consuming bifidobacteria improves outcomes in a rodent model of intestinal and metabolic disease. The significance of this project is that it will take a systematic and mechanistic approach to understanding the synbiotic relationship. RELEVANCE (See instmctions): The gut microbiome is a crucial component of human health. Safe and effective approaches for correcting, maintaining, and guiding establishment of a healthy gut microbiota, particularly in infancy and early childhood, are needed. The project is relevant to NCCAM's mission because it supports a portfolio of synbiotic interventions for improving health, with mechanistic signatures of biological effects.

项目总监/首席研究员（姓、名、中）：MIIIS、D a v l d 、A 。 项目摘要（参见说明）： 使用益生元和益生菌来恢复健康的肠道微生物群是一个理想的目标，但 缺乏特定细菌如何与肠道环境相互作用的机械相关特征 宿主阻碍了有效且特征良好的益生元和益生菌的开发 治疗。长期目标是转化哺乳动物哺乳的成功策略，使用 母乳聚糖，通过利用大量可用的母乳聚糖来开发有针对性的、有效的合生元 牛乳聚糖流。要测试的首要假设是进化关系 婴儿传播的双歧杆菌与牛乳聚糖和糖复合物之间产生协同作用 母乳聚糖样表型，可以有效地定植、恢复健康的肠道微生物群并诱导 宿主反应，以更好地保护上皮屏障功能，从而改善健康结果。一、团队 将解决婴儿传播的双歧杆菌物种中，复杂的乳糖复合物是否会诱导特定的 消耗这些复杂底物所必需的糖基水解酶和转运蛋白。牛奶 婴儿传播的双歧杆菌的糖复合物分解代谢将通过详细的转录组学进行检查， 特定酶和转运蛋白分析以及糖谱分析，以识别聚糖之间的精确联系 成分及其同源双歧杆菌加工机制。其次，研究团队将 确定是否选择消耗复杂乳糖复合物的婴儿传播双歧杆菌进行比较 单糖底物在诱导宿主上皮内的保护性反应方面更有效。 双歧杆菌粘附、屏障功能改善、炎症介质释放的测量 肠内分泌细胞的激活将在体外从肠上皮细胞和肠内分泌细胞获得 以及离体大鼠小肠和大肠组织。最后，团队将确定是否调制 通过应用合生乳聚糖和复合糖消耗双歧杆菌来改善肠道功能 改善肠道和代谢疾病啮齿动物模型的结果。该项目的意义在于 它将采取系统和机械的方法来理解合生关系。 相关性（参见说明）： 肠道微生物组是人类健康的重要组成部分。安全有效的纠正方法， 维持和指导建立健康的肠道微生物群，特别是在婴儿期和早期 童年，是需要的。该项目与 NCCAM 的使命相关，因为它支持一系列 用于改善健康的合生干预措施，具有生物效应的机械特征。