# Metabolic Regulation of Mucosal Inflammation

> **NIH VA I01** · VA EASTERN COLORADO HEALTH CARE SYSTEM · 2020 · —

## Abstract

The Inflammatory Bowel Diseases (IBD), including Crohn's disease and ulcerative colitis,
remain among the most debilitating inflammatory disorders of the western world. It is estimated
that more than 1.5 million Americans suffer with IBD, with incidence rates on the rise in many
populations. A recent study of more than 100,000 military service members estimated the
incidence of IBD to be 2-10 times greater than non-service members, with a striking relationship
between IBD incidence and the number of life stressors. The precise etiology of IBD is not known.
 Our interest is focused on the identification of inflammation-associated changes in tissue
metabolsim during flares of IBD. These studies are founded on the observation that active
intestinal inflammation in IBD is characterized by significant shifts in tissue metabolism that can
influence cell and tissue function in fundamental ways. Under such conditions, epithelial cells
have the capacity to dynamically control mucosal resolution and do so with a high degree of
fidelity. The precise mechanisms by which metabolic pathways control resolution, however, have
yet to be elucidated. Our work in progress has revealed that localized oxygen depletion (hypoxia)
during inflammation significantly influences the metabolic demands of the tissue. In ongoing work,
we have utilized global chromatin immunoprecipitation promoter arrays (ChIP-chip) in conjunction
with detailed metabolomics to identify tractable metabolite targets in intestinal epithelial cells that
control energy balance and barrier function. These studies have identified creatine and adenylate
energy intermediates as checkpoint metabolites in epithelial barrier regulation during
inflammation.
 In this proposal, we will define how epithelial metabolism molds the mucosal tissue
environment during inflammation. Three synergistic specific aims are directed at testing the
hypothesis that inflammation-associated changes within the tissue environment establishes
metabolic control of inflammatory resolution through the promotion of mucosal barrier function. In
Aim 1 will focus on defining the role of adenylate energy metabolism and AMP kinase activation in
barrier regulation within the mucosa. Aim 2 will elucidate the function of creatine transport in the
regulation of epithelial barrier function. Specific Aim 3 will elucidate the role of creatine transport
and adenylate energy metabolism in barrier regulation and wound healing in vivo. It is our hope
that these results will reveal new insights into innate regulation of mucosal inflammatory resolution
and that extensions of this work will lead to targets for experimental therapeutics.

## Key facts

- **NIH application ID:** 9832136
- **Project number:** 5I01BX002182-06
- **Recipient organization:** VA EASTERN COLORADO HEALTH CARE SYSTEM
- **Principal Investigator:** Sean P Colgan
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2014-04-01 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832136

## Citation

> US National Institutes of Health, RePORTER application 9832136, Metabolic Regulation of Mucosal Inflammation (5I01BX002182-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832136. Licensed CC0.

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