Activation of probiotic bifidobacteria by milk glyans

项目负责人/主要研究者（最后，第一，中间）：MIIIS，D a v l d，A。 项目总结（见说明）： 使用益生元和益生菌来恢复健康的肠道微生物群代表了期望的目标，但是， 缺乏特定细菌如何与肠道环境相互作用的机械相关特征 并且宿主阻碍了有效的和良好表征的益生元和益生菌的发展 治疗。长期目标是将哺乳动物哺乳的成功策略转化为 人乳聚糖，开发有针对性的，有效的合生元，通过使用丰富和可用的 牛乳聚糖流。有待检验的首要假设是， 在婴儿传播的双歧杆菌和牛乳聚糖和糖缀合物之间产生协同作用， 人乳聚糖样表型，其可以有效地定殖、恢复健康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。第一，团队 将解决是否在婴儿传播的双歧杆菌物种，复杂的牛奶糖缀合物诱导特异性 糖基水解酶和转运蛋白是消耗这些复杂底物所必需的。牛奶 通过详细的转录组学检查婴儿携带的双歧杆菌的糖缀合物催化剂， 特异性酶和转运蛋白分析以及糖谱分析，以确定聚糖之间的精确连接 组分及其同源生物降解细菌加工机制。第二，研究团队将 确定是否选择消耗复合乳糖缀合物的婴儿传播的双歧杆菌， 与单糖底物的结合更有效地诱导宿主上皮内的保护性反应。 生物粘附性、屏障功能改善、炎症介质释放的测量 肠内分泌细胞的活化将在体外从肠上皮细胞和肠内分泌细胞获得 和离体大鼠小肠和大肠组织。最后，该小组将确定是否调制 通过应用合生元乳聚糖和糖缀合物消耗双歧杆菌实现肠功能 改善肠道和代谢疾病啮齿动物模型的结果。这个项目的意义在于 它将采取系统和机械的方法来理解共生关系。 相关性（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，特别是在婴儿和早期 童年是需要的。该项目与NCCAM的使命相关，因为它支持以下组合： 合生素干预措施，以改善健康，与机械签名的生物效应。

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.