# Commensal fungal communities in the regulation of immunity and intestinal inflammation.

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $381,375

## Abstract

Abstract
Decades of research have revealed that intestinal bacteria are critical for regulating homeostatic and protective
immune responses. However, recent studies suggest that additional players such as fungi and viruses have also
the potential to influence these processes. It is unknown how gut fungal communities, so called “mycobiota”, can
be influenced by intestinal pathologies, antibiotic treatment, immune and dietary changes that have been
reported to lead to “bacterial dysbiosis”. We have shown that a polymorphism in the human gene encoding the
anti-fungal receptor Dectin-1 (CLEC7A) is strongly associated with the severity of ulcerative colitis (UC) and that,
in a mouse model of colitis, the overgrowth of opportunistic fungi such as Candida and Trichosporon spp.
contribute to intestinal inflammation. This suggests that disturbances in the healthy fungal community
(“mycobiota dysbiosis”) may be an important factor in the development or progression of intestinal disease. In
this proposal, we will explore the hypothesis that gut mycobiota dysbiosis might affect intestinal inflammation by
promoting aberrant interaction of “dysbiotic” fungi with the host mucosal immune system and with intestinal
bacteria. Our preliminary data show that mycobiota dysbiosis induced with the commonly used antifungal drug
fluconazole can affect the severity of lung allergy (house dust mite allergy model) and intestinal inflammation
(DSS and T cell transfer mouse models). Oral supplementation with three dysbiotic filamentous fungi (Aspergillus
amstelodami, Epicoccum nigrum, and Wallemia sebi) that expanded during fluconazole treatment recapitulated
the detrimental effects of fluconazole on inflammation, while fungi unrelated to dysbiosis (S. fibuligera) did not.
We found that, in addition to influencing the mycobiota, drug-induced dysbiosis affects gut bacterial communities.
In a novel “mycobiota defined” model that lacks indigenous fungi, introduction of a single intestinal fungus led to
distinctive changes in the intestinal bacteria, suggesting that fungi and bacteria can influence each other in the
gut. Employing new in vivo tools, high-throughput platforms and computational pipelines, we will focus on
delineating: (1) the mechanisms by which fungal dysbiosis affects gut mycobiota and intestinal inflammation, (2)
the relative contribution of Dectin-1 and adaptor molecule CARD9 on the inflammatory effects of mycobiota
dysbiosis, (3) the specific interactions of dysbiotic fungi with bacteria and with the host in a novel “mycobiota
defined” mouse model. It is currently unknown whether gut microbiota dysbiosis, which is solely viewed as
“bacterial dysbiosis”, is actually a collective feature of more complex interactions between prokaryotic and
eukaryotic communities. We anticipate defining how common antifungal drugs and dysbiotic fungi lead to
intestinal inter-kingdom community dysbiosis that affect immunity and contribute to intestinal disease. The results
of this...

## Key facts

- **NIH application ID:** 9900774
- **Project number:** 5R01DK113136-04
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ILIYAN Dimitrov ILIEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $381,375
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9900774

## Citation

> US National Institutes of Health, RePORTER application 9900774, Commensal fungal communities in the regulation of immunity and intestinal inflammation. (5R01DK113136-04). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/9900774. Licensed CC0.

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