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

> **NIH NIH R01** · UNIVERSITY OF MASSACHUSETTS AMHERST · 2022 · $338,643

## Abstract

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.

## Key facts

- **NIH application ID:** 10463744
- **Project number:** 5R01HD106554-02
- **Recipient organization:** UNIVERSITY OF MASSACHUSETTS AMHERST
- **Principal Investigator:** David A. Sela
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $338,643
- **Award type:** 5
- **Project period:** 2021-08-06 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463744

## Citation

> US National Institutes of Health, RePORTER application 10463744, Human milk urea nitrogen is recycled by Bifidobacterium infantis to impact the emergent physiology of the infant gut microbiome (5R01HD106554-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10463744. Licensed CC0.

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