# Nutrigenomics of Intestinal Vitamin D Action

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $692,807

## Abstract

Project Description
Vitamin D is an essential nutrient whose active hormonal form, 1,25-dihydroxyvitamin D (1,25(OH)2D), regulates
vitamin D receptor (VDR)-mediated gene expression to stimulate intestinal calcium absorption, to maintain
intestinal barrier function, to suppress colonic inflammation and to suppress carcinogenesis. However, intestinal
resistance to vitamin D develops with advancing age. This reduces intestinal Ca absorption in rodents and in
humans but it is not clear how age-associated intestinal vitamin D resistance affects other aspects of intestinal
vitamin D action. Thus, there is a critical knowledge gap regarding the mechanisms for how intestinal 1,25(OH)2D
action changes across the lifespan. Our long-term goal is to determine how vitamin D regulates intestinal
biology across the lifespan to modulate classical (Ca absorption) and non-classical (cancer, inflammation)
vitamin D endpoints. Our studies from the past grant period were the first to show the complexity of 1,25(OH)2D-
regulated gene regulation across the functional compartments of the intestine (i.e. small intestine (SI) crypt, SI
villus, colon). Our new preliminary data demonstrate that advanced age can suppress the intestinal induction of
some, but not all, vitamin D target genes. Thus, we hypothesize that age-related intestinal resistance to
1,25(OH)2D is due to context-dependent interference of VDR transcriptional mechanisms. To address this
hypothesis, we have designed three aims: Aim 1: Determine how 1,25(OH)2D genomic action is modified
across the lifespan to result in age-associated intestinal vitamin D resistance. Based on our pilot data, we
hypothesize that the impact of aging on vitamin D-dependent gene expression is not uniform across genes or by
intestinal compartment (i.e. SI/colon, crypt/villi). We will use state-of-the-art genomic approaches to study age-
and compartment-specific changes in intestinal vitamin D action. Aim 2: Determine how VDR genomic action
depends upon other transcription factors and co-regulators across the lifespan. We will conduct studies
to reveal the critical, VDR-interacting proteins that define compartment- and age-sensitive regulation of intestinal
gene expression and functionally test their roles in organoid models. Aim 3: Test whether targeting 1,25(OH)2D
to the proximal colon can enhance Ca absorption and reduce age-related bone loss. We will determine
whether colon-targeted forms of 1,25(OH)2D can enhance Ca absorption in mice to prevent trabecular bone loss
in adults and increased cortical porosity in old mice. Our proposed studies provide the unique opportunity to
determine (a) the scope of genes and regulatory regions impacted by aging in the intestine, (b) the role of
intestine-specific transcription factors and co-activators in age-associated intestinal vitamin D resistance, and (c)
whether colon-targeted forms of 1,25(OH)2D can have health benefits by overcoming age-associated vitamin D
resistance and Ca malabsorpt...

## Key facts

- **NIH application ID:** 10904400
- **Project number:** 2R01DK112365-05
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** SYLVIA S CHRISTAKOS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $692,807
- **Award type:** 2
- **Project period:** 2017-07-05 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904400

## Citation

> US National Institutes of Health, RePORTER application 10904400, Nutrigenomics of Intestinal Vitamin D Action (2R01DK112365-05). Retrieved via AI Analytics 2026-06-16 from https://api.ai-analytics.org/grant/nih/10904400. Licensed CC0.

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