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

母乳尿素氮被婴儿双歧杆菌回收，影响婴儿肠道微生物组的新兴生理学

• 批准号: 10298580
• 负责人: David A. Sela
• 金额: $ 33.92万
• 依托单位: UNIVERSITY OF MASSACHUSETTS AMHERST
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-06 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10298580
• 关键词: Address; Adult; Amino Acids; Ammonia; Basal metabolic rate; Bifidobacterium; Birth; Colon; Communities; Development; Diagnostic; Diet; Dietary Intervention; Goals; Health Promotion; Homeostasis; Human Milk; Immune system; In Vitro; Infant; Infant Health; Intervention; Knowledge; Life; Link; Mediating; Metabolic; Metabolism; Milk; Modeling; Molecular; Molecular Target; Neonatal; Nitrogen; Nursing infant; Nutrient; Nutritional; Nutritional status; Oligosaccharides; Pathway interactions; Phenotype; Physiological; Physiology; Play; Population; Recycling; Research; Role; Source; Structure; Systems Development; Testing; Urea; Urea Nitrogen; Urease; Vitamins; base; clinical investigation; dietary; gut colonization; gut microbiome; host-microbe interactions; in vitro Model; infant gut microbiome; infant nutrition; innovation; microbial; microbial community; microbial host; microbiome; microbiota; nitrogen metabolism; nutrition; pathogen; pre-clinical; targeted treatment; tool

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.

项目概要 母乳含有必需的营养物质和生物活性物质，它们通过什么途径转移给哺乳婴儿 曾经以线性方式考虑。尽管现在有大量证据表明母乳直接 通过调节特定的寡糖等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状态 与宿主的关系可能会影响生理机能。因此，尿素中结合的氮在 母乳中的浓度相对较高，可以通过宿主和共生体释放出来供其利用 微生物脲酶活性。我们假设尿素氮回收（UNS）是 生命早期的宿主-微生物相互作用。这对于处于这个关键阶段的婴儿来说可能特别重要 发育，或在膳食氮受到限制的宿主人群中。这个假设将得到解决 通过实验评估和表征婴儿相关共生体的代谢能力 利用尿素并将其转化为宿主可用的形式。此外，我们建议研究婴儿微生物组 在体外模型中建模介导的 UNS 来识别社区层面的现象。通过了解 尿素代谢对群落结构和功能的影响，我们将定义微生物组的标志 有效执行 UNS。 这项研究调查了一种鲜为人知的假设宿主-微生物相互作用，其影响 发育早期的氮稳态。王国间 UNS 途径可能至关重要 一般婴儿或某些营养环境下的婴儿。此外，本研究还进一步明确了什么是 基于总体群落功能的保护性婴儿微生物组。这可能会为诊断提供信息 评估 UNS 能力并制定干预措施以纠正次优的 UNS。如此一来，有目的的 UNS 的调节将增加指导微生物组功能的工具库，同时个性化 生命阶段、饮食和/或宿主表型。