Activation of probiotic bifidobacteria by milk glyans

项目主任/首席调查员(最后、第一、中间)：MIIIS，D a诉L d，A。 项目总结(见说明)： 使用益生菌和益生菌来恢复健康的肠道微生物区系是一个理想的目标，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 而宿主阻碍了有效且特性良好的益生菌和益生菌的发展 治疗。长期目标是将哺乳动物哺乳的成功策略转化为使用 人乳多糖，通过利用丰富和可用的方法开发靶向、有效的合生元 牛奶多糖流。需要检验的最重要的假设是进化关系 婴儿携带的双歧杆菌和牛乳之间的多糖和糖偶联物产生了协同作用 能有效定植、恢复健康肠道微生物区系并诱导 宿主反应，以更好地保护上皮屏障功能，从而改善健康结局。首先，团队 将解决在婴儿传播的双歧杆菌物种中，复杂的牛奶糖偶联物是否会诱导特异性 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 婴儿携带的双歧杆菌的糖共轭分解代谢将通过详细的转录组学进行检测， 特定的酶和转运蛋白分析，以及糖谱分析，以确定糖链之间的精确联系 成分及其同源双歧杆菌加工机制。第二，研究团队将 确定是否选择食用复合牛奶糖偶联物的婴儿传播的双歧杆菌进行比较 单糖底物在诱导宿主上皮内的保护性反应方面更有效。 双歧杆菌黏附、屏障功能改善、炎性介质释放的测量 肠上皮细胞和肠内分泌细胞在体外可获得肠内分泌细胞的激活。 并在大鼠小肠和大肠组织中进行体外实验。最后，团队将确定调制是否 应用共生乳糖及糖偶联物双歧杆菌的肠道功能 改善肠道和代谢性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(请参阅说明)： 肠道微生物群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区系，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，具有生物学效应的机械特征。

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.