# Role of Bacterial Urease in Host and Gut Microbiota Amino Acid Metabolism

> **NIH NIH K08** · UNIVERSITY OF PENNSYLVANIA · 2020 · $168,696

## Abstract

Project Summary
 Significant metabolic interactions exist between the gut microbiota and the mammalian host. These
interactions, mediated by the exchange of metabolites under environmental influences, are generally symbiotic
in nature, but can become detrimental in certain pathological states. One prime example is the delivery of urea,
a waste product from host nitrogen metabolism, into the colon and subsequent hydrolysis into carbon dioxide
and ammonia by the bacterial enzyme urease. The host can reabsorb the ammonia for additional nitrogen
metabolism, or the bacteria can use it for amino acid biosynthesis and contribute to host amino acid
homeostasis. In pathological conditions of hyperammonemia such as hepatic encephalopathy (HE) in liver
disease and urea cycle disorders, this process results in worsened morbidity and mortality. The pathogenesis
of HE is complex and not fully elucidated, and current treatments remain inadequate. We show that fecal
microbiota transplantation (FMT) using Altered Schaedler Flora (ASF), a defined consortium of eight murine
bacteria with minimal urease gene content, leads to improved neurobehavioral deficits and survival in the
thioacetamide (TAA) murine model of hepatic injury. The objective of this proposal is to characterize the
mechanism(s) by which ASF exerts its beneficial effects. The central hypothesis is that a urease-deficient
bacterial consortium such as ASF modulates nitrogen balance between the gut microbiota and its host leading
to an alteration in amino acid metabolism through urease-dependent mechanisms. This hypothesis will be
tested through three inter-related specific aims that will systematically evaluate the role of bacterial urease in
amino acid homeostasis in mice fed a normal protein diet (Aim 1), a low protein diet (Aim 2), and in the setting
of TAA-induced hepatic injury (Aim 3). The experiments will use various innovative approaches including
inoculation of a defined consortium composed of human bacterial strains that lack urease, heavy isotope 15N-
label studies, 16S rRNA gene microbiota sequencing, and murine metabolic phenotyping to address these
physiologically-relevant mechanisms. The proposed research is significant because it will provide new
information about the interaction between the gut microbiota and its host in the pathogenesis of HE, with the
rationale of improving treatment of HE through potential therapeutic FMT. University of Pennsylvania provides
the perfect research environment to conduct this investigation given local expertise in the inter-related fields of
gut microbiome and metabolism. The candidate will gain experience in compositional and functional analysis of
the microbiome, acquire fundamental skills in metabolomics and microbial isolation and culturing techniques,
and broaden his knowledge base of metabolic physiology. These skill sets will greatly enhance the candidate's
career development into an independent scientific investigator, with the long-term goal ...

## Key facts

- **NIH application ID:** 9931200
- **Project number:** 5K08DK106457-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ting-Chin David Shen
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,696
- **Award type:** 5
- **Project period:** 2017-07-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9931200

## Citation

> US National Institutes of Health, RePORTER application 9931200, Role of Bacterial Urease in Host and Gut Microbiota Amino Acid Metabolism (5K08DK106457-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9931200. Licensed CC0.

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