Human milk urea nitrogen is recycled by Bifidobacterium infantis to impact the emergent physiology of the infant gut microbiome

项目总结 母乳含有必需的营养物质和生物活性物质，它们在什么情况下转移给哺乳婴儿？ 曾被认为是线性的。尽管现在有相当多的证据表明，母乳可以引导 通过低聚糖等调节特定功能的分子早期建立微生物组 微生物种群。定植于胃肠道的微生物群落进入共生关系 与宿主的关系可能会影响生理。因此，尿素中结合的氮在 母乳中的浓度相对较高，可被释放出来供宿主和共生体利用 微生物尿素酶活力。我们假设尿素氮挽救(UNS)是一种关键的营养特性。 生命早期的宿主-微生物相互作用。在这一关键阶段，这可能对婴儿特别重要 发展，或在饮食氮有限的宿主种群中。这一假设将会得到解决。 通过实验评估和表征婴儿相关共生体的代谢能力 利用尿素，并由宿主将其转化为可用的形式。此外，我们建议研究婴儿微生物组- 在体外模型中对中介UNS进行建模，以确定社区水平的现象。通过理解 尿素代谢对群落结构和功能的影响，我们将定义一个微生物组的特征， 高效地执行UNS。 这项研究调查了一种鲜为人知的和假想的宿主-微生物相互作用，这意味着 发育早期的氮素平衡。跨王国UNS途径可能对 一般情况下或某些营养状况下的婴儿。此外，这项研究还进一步定义了什么构成 基于聚集体功能的婴幼儿微生物群保护性研究。这可能会通知诊断学 评估联合国后勤基地的能力，并制定干预措施以纠正不太理想的联合国后勤基地。因此，有目的的 UNS的调整将增加指导微生物组功能的工具库，同时个性化 生活期、饮食和/或寄主表型。

PROJECT SUMMARY Human milk contains essential nutrients and bioactives that are transferred to the nursing infant in what was once considered in a linear manner. Though now there is considerable evidence that human milk directs early establishment of the microbiome through molecules such as oligosaccharides that modulate specific microbial populations. Microbial communities that colonize the gastrointestinal tract enter into a commensal relationship with their host potentially impacting physiology. Accordingly, nitrogen bound in urea is delivered at relatively high concentrations in breast milk and may be liberated for utilization by the host and commensals by microbial urease activity. We hypothesize that urea nitrogen salvaging (UNS) is a key syntrophic feature of host-microbial interactions early in life. This may be of particular importance to infants in this critical stage of development, or in host populations where dietary nitrogen is limiting. This hypothesis will be addressed experimentally by evaluating and characterizing the metabolic capacity for infant-associated commensals to utilize urea and transform it to a usable form by their host. Moreover, we propose to study infant microbiome- mediated UNS modeled in an in vitro model to identify community-level phenomena. By understanding the impact to community structure and function by urea metabolism, we will define hallmarks of a microbiome that performs UNS efficiently. This study investigates a poorly understood and hypothetical host-microbial interaction with implications to nitrogen homeostasis early in development. The inter-kingdom UNS pathway may be of critical importance to infants in general or in certain nutritional contexts. In addition, this study further defines what constitutes a protective infant microbiome based on aggregate community function. This would potentially inform diagnostics to assess UNS capacity as well as develop interventions to correct suboptimal UNS. As such, purposeful modulation of UNS would increase the repertoire of tools to direct microbiome function while personalizing for life stage, diet, and/or host phenotype.