# Metabolic Regulation of Inflammation by Microbial-Derived Short Chain Fatty Acids

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $377,022

## 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. The precise etiology of IBD is not known.
 Our interest is focused on the identification of inflammation-associated changes in tissue
metabolism during active inflammation. In particular, we aim to better understand how microbial-
derived factors, such as short chain fatty acids (SCFA), contribute to mucosal barrier function and
wound healing. Our work in progress has focused on defining molecular pathways and microbial
targets associated with metabolic shifts in inflammation. In ongoing work using unbiased single
cell RNA sequencing (scRNAseq), we identified a cohort of butyrate-induced genes with potential
importance in barrier function and mucosal wound healing responses. This butyrate-elicited
epithelial gene signature serves as a template to understand host-microbial interactions at a
molecular level.
 In this proposal, we will define how microbe-derived SCFA are essential for integrated
epithelial functional responses that promote barrier function and coordinate wound healing. Three
synergistic specific aims are proposed. In Aim 1, we will elucidate the contribution of butyrate-
induced target gene(s) to barrier formation and wound healing. Aim 2 will define the relative
contribution of HIF stabilization and/or HDAC inhibition to SCFA-elicited mucosal barrier function
and wound healing. Specific Aim 3 will determine the relevance of butyrate-induced signaling and
gene expression in acute and chronic mucosal inflammation models in vivo. Results from these
experiments will provide new insights into innate regulation of mucosal barrier and an expanded
physiological role for SCFA produced by commensal bacteria. It is our hope that extensions of this
will lead to the identification of new therapeutic targets for mucosal inflammatory disease

## Key facts

- **NIH application ID:** 9897168
- **Project number:** 2R01DK104713-06
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sean P Colgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $377,022
- **Award type:** 2
- **Project period:** 2015-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897168

## Citation

> US National Institutes of Health, RePORTER application 9897168, Metabolic Regulation of Inflammation by Microbial-Derived Short Chain Fatty Acids (2R01DK104713-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9897168. Licensed CC0.

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