# Microbiota metabolites SCFA promote intestinal epithelial repair and wound healing

> **NIH NIH F30** · UNIVERSITY OF TEXAS MED BR GALVESTON · 2021 · $34,626

## Abstract

ABSTRACT
Inflammatory bowel disease (IBD) is a sizable health challenge that has emerged in the 21st century, affecting
millions of people worldwide with incidence rates on the rise. Current therapies are insufficient to induce long-
term remission in many patients, leading to high rates of surgical intervention and increased risk of colorectal
cancer (CRC). Thus, new therapies are needed to decrease morbidity and mortality from IBD. Many patients
with IBD are deficient in the microbial metabolites of dietary fibers, short chain fatty acids (SCFAs), and thus
SCFAs represent a potential target for therapeutic development. SCFAs play complex roles in gut homeostasis
including epithelial turnover, proliferation, apoptosis, and immune regulation. SCFAs have a profound impact
on human health and disease, and a diet high in dietary fibers has been linked to decreased risk of CRC and
IBD. To date, the evidence for use of SCFAs as a treatment for IBD has been inconsistent. These
inconsistencies are most likely driven by SCFAs ability to regulate gene expression by inhibition of histone
deacetylases; however, which genes are differentially regulated is largely dependent on the type of SCFA, its
concentration relative to other SCFAs, and the cell type, all of which further complicate treatment. To date, the
identity of the specific genes that are differentially regulated by SCFAs to induce wound healing and modulate
inflammation are unknown. Recently, we identified a secreted glycoprotein, milk fat globule-EGF factor 8
(MFGE8), which is significantly upregulated by SCFAs. MFGE8 is deficient in IBD patients, and plays roles in
cellular migration and T cell differentiation. Thus, the long-term goal of this project is to understand the role of
SCFAs in the promotion of migration and suppression of inflammation, key processes in wound healing and
protection against colitis. Our hypothesis is that SCFAs differentially regulate intestinal epithelial cell
(IEC) expression of MFGE8 to induce wound healing and suppress inflammation in IBD. Using MFGE8
deficient cell lines and KO mice, we will employ several molecular biology techniques including wound healing
assays, immunohistochemistry, confocal microscopy, kinase assays, ex. vivo enteroid cultures, flow cytometry,
and acute and transfer models of experimental colitis to address our hypothesis through two specific aims: 1)
Define the role of MFGE8 in SCFA-induced wound healing; 2) Determine SCFA conditioning of IEC to
induce Treg development through induction of MFGE8. Elucidating the roles of MFGE8 in SCFA induction
of wound healing and suppression of inflammation in IBD will help deepen our understanding of the potential of
SCFAs as a therapeutic. This information will be utilized to inform future therapeutic development involving
SCFAs, and ultimately remove a critical barrier that is preventing long-term sustained remission in a large
percentage of IBD patients.
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## Key facts

- **NIH application ID:** 10106622
- **Project number:** 5F30DK120212-03
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **Principal Investigator:** Anthony J Bilotta
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $34,626
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10106622

## Citation

> US National Institutes of Health, RePORTER application 10106622, Microbiota metabolites SCFA promote intestinal epithelial repair and wound healing (5F30DK120212-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10106622. Licensed CC0.

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