# Inflammatory cross-talk between skin and gut

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $676,015

## Abstract

Project Summary/Abstract
Inflammatory bowel diseases are frequently complicated by diseases of the skin. It is not understood why
disease of the surface epithelial tissues of the skin influences the severity of disease of the very different
barrier epithelia in the gut. This proposal will test the central hypothesis that the “inflammatory cross” talk
between skin and the intestine is a consequence of release of hyaluronic acid (HA) from the extracellular
matrix of the skin that then promotes reactive adipogenesis of the intestinal submucosa. Reactive
adipogenesis is a newly recognized innate immune response in both skin and intestine, and important for
antimicrobial defense. Our preliminary data will show that skin injury, or targeted expression of hyaluronidase
in the skin, has a major affect on the intestinal stroma, resulting in alterations in gut inflammation and the fecal
microbiome. The mechanism we propose to explain how this occurs centers around our discovery that HA is
key for the capacity of submucosal intestinal fibroblasts to differentiate into adipocytes. Fragments of HA
generated in the skin circulate to the gut to stimulate adipogenesis and induce transcriptional changes in
preadipocytes. The stromal cells undergoing differentiation into adipocytes and then release antimicrobial
peptides and adipokines that alter the immune status of the intestine. Thus, our central hypothesis is that injury
to the skin modulates host defense in the intestine by the capacity of HA fragments to stimulate adipocyte
differentiation. This proposal will test this hypothesis, carefully define the influence of adipogenesis on local
host defense and define the mechanisms responsible for these observations. This data can be critical toward
developing new and innovative treatments for intestinal inflammation.

## Key facts

- **NIH application ID:** 10570908
- **Project number:** 5R01DK128787-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Richard L Gallo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $676,015
- **Award type:** 5
- **Project period:** 2021-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10570908

## Citation

> US National Institutes of Health, RePORTER application 10570908, Inflammatory cross-talk between skin and gut (5R01DK128787-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10570908. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*