# Mechanisms associated with flares and remission in colitis

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $701,092

## Abstract

Summary
Inflammatory bowel diseases (IBD) affect millions of individuals worldwide and its incidence is increasing. Both
genetic and environmental factors appear to play a role in IBD development. Genetic studies in humans have
linked the interleukin-23 (IL-23) signaling pathway with IBD, but the environmental factors contributing to disease,
have remained elusive. The rising incidence of worldwide IBD has been associated with westernization of dietary
habits in developing countries, however there is little scientific evidence to support causality. In this application
we will examine the role of a particular group of dietary additives, namely food colorants, to development of
colitis. We have now discovered that the food colorant Red 40, also known as Allura Red AC, promotes colitis
in mice that conditionally express low levels of IL-23 (referred to as R23FR mice), but not in wild type mice. Red
40 is the most abundant food colorant in the world, with annual production exceeding 2.3 million kg. It is widely
used in as red colorant in soft drinks, cherry flavored products, candy, dairy, drugs, and cosmetics. Of interest,
the Red 40-containing beverages, Kool-Aid and the hydrating solution Pedialyte Cherry can also cause colitis in
R23FR mice. Red 40-induced colitis in R23FR mice requires the microbiota and CD4+ T cells. Based on these
and other results presented here, we formulate a central hypothesis that the Red 40 or its metabolites haptenize
bacterial or endogenous proteins to generate tolerance in wild type mice, or colitis in mice in which IL-23
expression is dysregulated. We will study in this proposal the mechanisms involved in generation and prevention
of these responses. Specifically, we will define: 1) if Red 40 and its metabolite ANSA are haptens; 2) how Red
40 induces tolerance in control mice; and 3) if Red 40 or ANSA-specific T cells are generated in R23FR mice

## Key facts

- **NIH application ID:** 10438874
- **Project number:** 5R01DK110352-06
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** SERGIO A. LIRA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $701,092
- **Award type:** 5
- **Project period:** 2017-05-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438874

## Citation

> US National Institutes of Health, RePORTER application 10438874, Mechanisms associated with flares and remission in colitis (5R01DK110352-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438874. Licensed CC0.

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