# Vitamin D Receptor Regulation of Microbiota in Intestinal Epithelia

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2024 · $576,573

## Abstract

Abstract
Inflammatory bowel diseases (IBD) occur when there is an unfortunate combination of microbial dysbiosis and
genetic susceptibility. Downregulation of Vitamin D receptor (VDR), a host factor, promotes the severity, extent,
and duration of mucosal inflammation and dysbiosis. However, most studies examining gut microbiota have
primarily relied on fecal or colonic luminal samples. In contrast, few studies have considered the roles of the
small intestinal microbiome. Classically, Paneth cells located in the small intestine are a significant source of
antimicrobial peptides (AMPs) and proteins important in host defense. Although Paneth cells are located in the
small intestine, AMPs are released to the entire intestine, thus shaping the gut microbiome. VDR regulation of
gut bacterial pathogenesis has become an emerging area in IBD, however, the aspect of small intestinal
microbiome and metabolites has yet to be explored. Given the challenges in treating patients with Crohn’s
disease and the limited studies on the small intestinal microbiome, it is critical to understand how Paneth cell
VDR is involved in microbial homeostasis, balanced metabolites, and innate immunity. The objective of our
current R01 proposal is to study regulatory mechanisms of Paneth cell VDR and to restore microbiome /
metabolites in inflamed states. Our preliminary data showed Paneth cell VDR conditional knockout (VDRΔPC)
leads to dysbiosis and susceptibility to Salmonella-induced colitis. We established a method to purify Paneth
cells and study their alertness to bacterial pathogens. Furthermore, conditional VDR deletion severely changed
the metabolite profile. However, the complex mechanisms in the ileitis through the Paneth cell VDR are still
unknown. We hypothesize that VDR deficiency in Paneth cells alters the microbiome/metabolites and
makes the host susceptible to chronic intestinal inflammation (e.g., ileitis). We have designed two Aims to
rigorously examine the hypotheses at the cellular and microbiome levels: Aim 1. Define the mechanism by which
VDR maintains healthy Paneth cells and impacts ileitis inflammation. Aim 2. Investigate the role of Paneth cell
VDR in altering the microbiome / metabolites and define the mechanism of VDR in restoring microbial
homeostasis, when administering microbiome via fecal transplantation or recolonization in originally germ-free
mice. Specifically, we will use novel animal models, organoids from human IBD biopsies, and statistical and
bioinformatic tools to understand the host factors and aspects of microbiome / metabolites in chronic intestinal
inflammation. Our research team includes experts in the following areas: epithelial biology, animal models,
clinical gastroenterology, and microbiome. Our studies are innovative because we provide a unifying
hypothesis that can potentially account for defective a host factor in VDR signaling pathway, abnormal Paneth
cells, and dysbiosis in IBD. Cutting edge technologies and models will be...

## Key facts

- **NIH application ID:** 10919835
- **Project number:** 5R01DK134343-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Jun Sun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $576,573
- **Award type:** 5
- **Project period:** 2023-09-15 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919835

## Citation

> US National Institutes of Health, RePORTER application 10919835, Vitamin D Receptor Regulation of Microbiota in Intestinal Epithelia (5R01DK134343-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10919835. Licensed CC0.

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