# The Intestinal Mycobiome and IBD

> **NIH NIH K01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $121,770

## Abstract

PROJECT SUMMARY
Crohn’s disease (CD) represents a significant public health challenge with more than 1 million individuals
affected by this condition in the US. To date, a complete cure of CD is not available. CD has a multifactorial
etiology, characterized by a complex interplay between environmental and genetic factors, particularly an
inappropriate inflammatory response to commensal microbes in genetically affected individuals.
Fungal infection
represents one of the most serious health hazards, especially for immuno-compromised patients.
C
andidiasis
has dramatically increased worldwide, especially in neutropenic patients or patients with altered gut microbiome
due to increased antibiotic use. Recent studies performed by our group have demonstrated that the abundance
C. tropicalis is significantly higher in patients with CD compared to their non-diseased first-degree relatives. C.
tropicalis and C. albicans have been recognized as the most common pathogenic fungi and are part of the human
commensal flora. C. tropicalis and C. albicans are commonly found in the gastrointestinal tract. However, the
role of Candida infections in intestinal inflammation in patients with CD has not been fully elucidated. Therefore,
there is a need for mechanistic studies aimed at delineating the molecular mechanisms by which Candida
infection may result in exacerbation of CD. Studies proposed herein take advantage of a unique resource, a
spontaneous murine model of CD-like ileitis (SAMP1/YitFc or SAMP), to decipher the mechanistic role of
candidiasis in experimental ileitis. Strong preliminary data from our group have demonstrated that C57BL/6 (B6)
mice infected with C. tropicalis are significantly more susceptible to develop dextran sodium sulfate (DSS)-
induced colitis compared to uninfected littermates, with increased gene expression of key Th1 response-
associated genes, such as Tnf and Ifn, and decreased expression of Th2 response-associated genes, such
as Il4 and Il13. 16S rRNA analysis of fecal samples from infected and uninfected mice have shown that C.
tropicalis significantly altered the microbiome population of B6 mice, with increased abundance of mucin
degrading bacteria, such as Akkermansia (A.) muciniphila and Ruminococcus (R.) gnavus.
Based on its
biological effects, we hypothesized that Candida infection may alter the gut microbiome community resulting in
dysbiosis that, in turn, increases the susceptibility of the host to develop IBD, or triggers flare in CD patients. The
goals of this proposal are: (1) demonstrate that Candida infections contribute to worsen experimental intestinal
inflammation; and (2) identify the specific microbes and mechanisms responsible for the increased intestinal
inflammation in B6 and SAMP mice. Understanding the mechanisms by which candidiasis affects the gut
microbiome is essential to maintain remission in CD patients and the design of novel antimicrobial therapies with
increased efficacy and decreased side-effects.

## Key facts

- **NIH application ID:** 10337333
- **Project number:** 5K01DK125526-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Luca Di Martino
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $121,770
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10337333

## Citation

> US National Institutes of Health, RePORTER application 10337333, The Intestinal Mycobiome and IBD (5K01DK125526-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10337333. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*