# Metabolic Regulation of Inflammation by Microbial SCFA

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2024 · $500,301

## Abstract

PROJECT 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 3 million
Americans suffer with IBD, with incidence rates on the rise in many populations. The precise etiology of IBD
is not known but emerging evidence implicates shifts in the constellation of microbes in the intestine
(dysbiosis) as a significant factor.
 Our interest in this proposal is aimed at capitalizing on the importance of microbiota- derived
metabolites in promoting intestinal homeostasis. In particular, we aim to better understand how microbial-
derived factors, such as short chain fatty acids (SCFA, esp. butyrate), contribute to mucosal barrier function
and wound healing. Our work in progress has focused on developing and testing a panel of butyrate
mimetics that may best serve mucosal barrier function and wound healing in models of IBD. Additional
ongoing work using unbiased single cell RNA sequencing (scRNAseq), we identified a cohort of butyrate-
induced genes with potential importance in barrier function.
 In this proposal, we will elucidate whether butyrate mimicry can elicit selectively integrated epithelial
functional responses that promote barrier function and coordinate wound healing. Three synergistic specific
aims are proposed to address this goal. In Aim 1, we will expand on molecular mimicry of butyrate analogs to
optimize epithelial function. Aim 2 will elucidate the mechanisms of selective epithelial control butyrate
analogs. Specific Aim 3 define disease-relevant influences of butyrate mimicry on 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 work will lead to the discovery of new
therapeutic templates for mucosal inflammatory disease.

## Key facts

- **NIH application ID:** 10981021
- **Project number:** 2R01DK104713-10
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Sean P Colgan
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $500,301
- **Award type:** 2
- **Project period:** 2015-04-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10981021

## Citation

> US National Institutes of Health, RePORTER application 10981021, Metabolic Regulation of Inflammation by Microbial SCFA (2R01DK104713-10). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10981021. Licensed CC0.

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