# Vitamin A metabolizing activity of the gut microbiome.

> **NIH NIH R21** · BROWN UNIVERSITY · 2022 · $212,542

## Abstract

Project Summary:
The human and mouse colonic microbiota is a large and complex microbial community. The gene
set of the gut microbiota (the gut microbiome) is estimated to be about 3 million genes ~150 times
larger than that of the human genome. This large and diverse microbial community has an equally
extensive metabolic repertoire that complements the activity of mammalian enzymes in the liver
and gut mucosa however its role in metabolizing intestinal vitamin A has not been
explored. Vitamin A, a diet derived nutrient, is key for regulating multiple aspects of immunity and
susceptibility to infections. Effect of vitamin A are coordinated via its metabolite retinoic acid (RA),
a potent regulator of cellular transcriptional program. RA signaling in the lymphocytes is required
for initiating transcriptional programs that guide their homing to the mucosal tissue as well their
cell-fate transitions in the intestinal mucosa. Additionally, RA signaling is critical for maintaining
plasticity of intestinal epithelium, allowing them to dedifferentiate and replenish the pool of cycling
cells that are lost upon damage. We find that gut lumen of conventional mice has much higher
RA levels while in germ-free state RA levels are undetectable in the lumen. Moreover, we find
that gut bacteria show strong activity for aldehyde dehydrogenase, a key rate limiting enzyme that
is responsible for conversion of vitamin A to RA. Finally, we identify Lactobacillus spp in the mouse
gut microbiome as bacterial taxa possessing vitamin A metabolic activity. We hypothesize that
gut microbiome is a novel and potent source of vitamin A metabolic activity that plays a
crucial role in regulating levels of metabolically active retinoids in the gut and regulates
vitamin A dependent host physiology in the intestine and beyond. In this proposal we will
explore the potential of gut microbiome to metabolize dietary vitamin A into RA and its effect on
the mammalian host.

## Key facts

- **NIH application ID:** 10539433
- **Project number:** 1R21AI168772-01A1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Shipra Vaishnava
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $212,542
- **Award type:** 1
- **Project period:** 2022-05-25 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10539433

## Citation

> US National Institutes of Health, RePORTER application 10539433, Vitamin A metabolizing activity of the gut microbiome. (1R21AI168772-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10539433. Licensed CC0.

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