# Regulation of the mycobiota and intestinal inflammation via production of antifungal metabolites by commensal bacteria

> **NIH NIH F32** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $67,446

## Abstract

Project Summary
 The human intestinal tract supports a complex microbial environment consisting of bacterial (or
microbiota) and fungal (or mycobiota) constituents. Although the role of each of these organisms in eliciting
immune activation and inflammation in the gut has begun to be investigated and appreciated by the larger
scientific community, their interspecies interactions within the context of the gastrointestinal tract remains an
underrepresented area of research. The chemical basis for such interactions, critical for the rational design of
treatments in gastrointestinal infection and disease, remain completely uncharted territory in the literature. This
lies in stark contrast to the vibrant fields of terrestrial and marine secondary metabolite structural determination
and bioactivity, where a seemingly endless stream of biosynthesized natural products and effector pathways
been elucidated between fungi and bacteria. Our preliminary ribosomal 16S sequencing data show that
specific communities of anaerobic bacteria are drastically increased in a reproducible way with a variety of
antifungal medications. This analysis indicates that bacteria and fungi may occupy a similar, competitive
ecological niche within the gut ecosystem. To illuminate the potential for bacterial metabolites to influence the
mycobiota, thereby establishing a competitive advantage, we developed a library of known gut metabolites and
screened for antifungal activity at physiologically relevant conditions in vitro. This resulted in the identification
of two metabolites of bacterial origin with antifungal activity. Additionally, the work of our lab and others has
shown that species-level diversity in the mycobiota is lost during inflammatory bowel disease (IBD) in the
human gut and outgrowth of the opportunistic fungal pathogen Candida albicans (C. albicans) is observed. We
therefore hypothesize that opportunistic pathogenic fungi are held in check by bacterial metabolite production
and that this mechanism is stimulated by intestinal fungi and impacts gastrointestinal inflammation. In addition
to revealing novel mechanisms of fungal-bacterial interaction at an unprecedented small molecule level, the
results of this proposed investigation will illuminate how fungal dysbiosis impacts the etiology and progression
of intestinal inflammation, illuminating potential new strategies for the treatment of gastrointestinal diseases.

## Key facts

- **NIH application ID:** 9868196
- **Project number:** 5F32DK120228-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** William D Fiers
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2019-01-25 → 2022-01-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9868196

## Citation

> US National Institutes of Health, RePORTER application 9868196, Regulation of the mycobiota and intestinal inflammation via production of antifungal metabolites by commensal bacteria (5F32DK120228-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9868196. Licensed CC0.

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