# Polymicrobial interactions in Crohn's Disease

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $617,403

## Abstract

The role of gut fungal community (“mycobiome”, MYC) and interactions between the bacteriome (BM) and fungal
communities in Crohn’s Disease (CD) have been relatively ignored. Recently, we compared the gut BM and MYC
of CD patient’s to their healthy relatives and showed that abundance of the fungus Candida tropicalis (CT) was
positively correlated with the bacteria Serratia marcescens (SM) and Escherichia coli (EC).
We analyzed the
number of CD patients that had all 3 species; the number CD patients exhibiting all 3 organisms was 30%,
compared to 9% in healthy controls. Critically, abundance of all three organisms is 6.2 fold higher in CD patients
vs. controls. Thus, the prevalence of this combination of microorganisms in the GI tracts of CD patients is significant.
We further showed that ex-vivo, these polymicrobial triple species cooperated to form robust biofilms (TSBs) that
were significantly increased compared to those formed by single-species (SSBs) or double-species (CT+EC or
CT+SM, DSBs). Supporting data showed the interaction between CT, SM, and EC was specific; substitution of
Trichosporon spp. (TC) or Saccharomyces fibuligera (SF) did not increase biofilm formation. However, preliminary
data using Candida albicans (CA) as a control comparator reported by others to be elevated in CD patients, did
cause increased TSB biofilm formation, indicating that this is a Candida specific effect. Importantly, we validated
that the 3 pathogens formed robust biofilms in vivo (an anaerobic environment) using a dextran sodium
sulfate (DSS) model of murine ulcerative colitis. Metabolomic analyses of supernatants from TSBs identified 11
significantly increased metabolites compared to SSBs or DSBs. Of these, 5-oxoproline (5-OP), was the most
elevated metabolite (131-fold higher in TSBs compared to SSBs or DSBs). Also, Indole-3-acetic acid (IAA), formed
as a result of Lactobacilli metabolizing tryptophan, which can act as an endogenous ligand for aryl hydrocarbon
receptors (AhR), mediating innate lymphoid cell (ILC) production of IL-22, that in-turn triggers the inhibition of CA
colonization, was also significantly increased. These 2 metabolites influence candidal virulence factors
(filamentation, adhesion and auto-aggregation). Although these data are significant and indicate a strong
polymicrobial interaction in CD, they do not establish the underlying mechanisms of these microbial interactions.
This proposal focuses on determining the mechanism/s underlying the interaction of mixed species microbes using
complementary in vitro and in vivo approaches.
Our hypothesis is that SM, EC and Candida (CT and CA), in the
setting of biofilms, interact cooperatively to exacerbate intestinal inflammation and exacerbate symptoms
 To address the mechanism(s) we will: (1) Determine the mechanism(s)
metabolites formed by CT, EC, and SM in TSBs alter intestinal outcomes; (2) Identify gene changes
underlying Candida modifications that increase pathogenicity using microbial ...

## Key facts

- **NIH application ID:** 10223109
- **Project number:** 5R01AI145289-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Mahmoud A Ghannoum
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $617,403
- **Award type:** 5
- **Project period:** 2019-07-08 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10223109

## Citation

> US National Institutes of Health, RePORTER application 10223109, Polymicrobial interactions in Crohn's Disease (5R01AI145289-03). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10223109. Licensed CC0.

---

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