# Targeting the Mycobiome in Genetically Defined Patients with Crohns Disease

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2023 · $633,061

## Abstract

ABSTRACT
Inflammatory bowel disease (IBD), divided largely into Crohn’s Disease (CD) and ulcerative colitis, is a chronic
and serious disease that results from dysregulated inflammatory immune activity in the mucosa of the
gastrointestinal tract. There has been much progress defining genetic, intestinal microbiome, host pathway, and
environmental roles in disease, and a major goal in IBD research and care is to translate these observations into
strategies to improve outcomes by better matching disease treatment with patients’ specific underlying
mechanisms of disease.
Studies on the role of the microbiome in influencing IBD have focused largely on the bacterial microbiota, while
the potential role for commensal fungal microbiota to influence disease has been largely overlooked. We recently
reported a strong association of the yeast Malassezia with Crohn’s Disease. Specifically, intestinal mucosa-
associated Malassezia are elevated in patients carrying a previously described IBD risk polymorphism (S12N)
in the gene for CARD9, a signaling molecule require for antifungal inflammatory immune responses. In mouse
models, Malassezia exacerbates colitis via a mechanism requiring CARD9. This project is designed to test the
hypothesis that oral antifungal treatment can reduce the burden of Malassezia spp. in CD patients with the
CARD9 S12N allele and improve disease symptoms. The approach includes a two-center randomized, double-
blind, placebo-controlled study of antifungal drug treatment in genetically defined patients with active Crohn’s
disease. We will evaluate the consequences of antifungal drug treatment on the overall microbiome and
metabolites it produces as well as regulation of immune cell function in the mucosa.

## Key facts

- **NIH application ID:** 10598044
- **Project number:** 5R01DK125495-03
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** Gil Y Melmed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $633,061
- **Award type:** 5
- **Project period:** 2021-05-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10598044

## Citation

> US National Institutes of Health, RePORTER application 10598044, Targeting the Mycobiome in Genetically Defined Patients with Crohns Disease (5R01DK125495-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10598044. Licensed CC0.

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