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.

项目摘要 母乳含有必需的营养素和生物活性物质，它们通过什么方式转移到哺乳期婴儿身上？ 曾经被认为是线性的。尽管现在有大量证据表明母乳会直接 通过调节特异性的寡糖等分子早期建立微生物组 微生物种群定植在胃肠道的微生物群落进入肠道， 与宿主的关系可能会影响其生理机能因此，结合在尿素中的氮以约100%的速率递送。 母乳中的浓度相对较高，可通过以下方式释放供宿主和哺乳动物利用： 微生物脲酶活性我们假设尿素氮回收（UNS）是一个关键的互养特征， 宿主与微生物的相互作用这对处于这一关键阶段的婴儿来说可能特别重要。 发展，或在宿主种群中，膳食氮是有限的。这一假设将得到解决 通过评估和表征婴儿相关的代谢能力， 利用尿素并将其转化为可供宿主使用的形式。此外，我们建议研究婴儿微生物组- 介导的UNS在体外模型中建模，以识别社区水平的现象。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特征， 有效地执行UNS。 这项研究调查了一个知之甚少和假设的宿主-微生物相互作用， 氮稳态早期发展。王国间的UNS途径可能对 一般情况下或在某些营养环境下的婴儿。此外，本研究还进一步界定了 保护性的婴儿微生物组基于聚集的社区功能。这可能会告知诊断 评估联合国系统的能力，并制定干预措施，以纠正不理想的联合国系统。因此，有目的 UNS的调制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。