# Microbial provision of essential amino acids: protein conservation in hibernation

> **NIH NIH P20** · UNIVERSITY OF ALASKA FAIRBANKS · 2020 · $189,413

## Abstract

Project Summary Project 2 – Microbially-liberated urea nitrogen and host essential amino acids.
The elderly are particularly susceptible to sarcopenic obesity (SAO), whereby a loss of lean mass (e.g.,
muscle) accompanies an increase in fat, and which is difficult to treat via life style changes (e.g., diet) designed
to target obesity. Although numerous studies have addressed the role of diet and gut microbes as factors in
diseases such as obesity, the potential beneficial role of gut microbes in preventing loss of lean mass in
disorders such as SAO has received comparably less attention. Urea-nitrogen salvage (UNS) is the process
whereby urea is degraded by gut microbes releasing nitrogen that can be utilized by gut microbes to produce
amino acids, or be reabsorbed and used by the host. UNS likely plays an important role in nitrogen metabolism
in humans, and evidence suggests both UNS and the production of essential amino acids (EAAs) by gut
microbes may have important impacts on human health. Yet, despite the availability of microbially-liberated
urea-nitrogen (MLUN) for EAA synthesis in the gut, these two microbial components of host nitrogen
metabolism have been studied primarily independently and with little focus on the structure and function of the
gut microbial community. The goal of this project is to determine the gut microbiota potential for use of MLUN
in synthesis of EAAs, and demonstrate the provision of microbially-synthesized EAAs for host protein
synthesis. We use the arctic ground squirrel (AGS) as a study species, as AGS are able to preserve lean mass
during their long hibernation season. Our hypothesis is that MLUN in the gut of AGS is utilized by gut microbes
for synthesis of EAAs which are incorporated into host tissues during hibernation. Our approach relies upon
simultaneous analyses of the structure and function of the gut microbial community, microbial production of
EAAs using MLUN, and incorporation of microbial-derived EAAs in host tissues under varying conditions of
host dietary protein availability and physiological state. In Specific Aims 1 and 2 we utilize isotopically labeled
urea (13C and 15N), which when injected intra-peritoneally diffuses into the gut and becomes available for
urea degrading microbes. After injecting hibernating squirrels with labeled urea, we will measure 13CO2 in
breath (to confirm ureolytic activity), determine the EAA synthesis potential of the gut microbiota using next
generation sequencing techniques (metagenomics and metatranscriptomics to look for EAA biosynthesis
genes) and metabolomics (15N-NMR to search for labeled EAAs in gut contents), and determine if AGS
incorporate microbially-derived EAAs into host tissues (15N-NMR). In Specific Aim 3, we will isolate and
characterize bacteria from the GI tract of AGS and determine culture conditions necessary for growth to
experiment with mock gut communities in the future. Our approach promises to yield an increased knowledge
of the role of t...

## Key facts

- **NIH application ID:** 9978876
- **Project number:** 5P20GM130443-02
- **Recipient organization:** UNIVERSITY OF ALASKA FAIRBANKS
- **Principal Investigator:** Khrystyne Duddleston
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $189,413
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978876

## Citation

> US National Institutes of Health, RePORTER application 9978876, Microbial provision of essential amino acids: protein conservation in hibernation (5P20GM130443-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9978876. Licensed CC0.

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