# Investigation of commensal bacteria-produced metabolites with activity towards mycobiota.

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $211,875

## 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 as well as their ability to initiate systemic infection 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 have 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 activity towards
opportunistic members of the mycobiota. We therefore hypothesize that opportunistic pathogenic fungi in the
gut are held in check by bacterial metabolite production and that this mechanism is stimulated by intestinal
fungi to impact infectious states. In addition to revealing novel mechanisms of fungal-bacterial interaction at an
unprecedented small molecule level, the results of this proposed investigation will illuminate potential new
strategies for targeting of fungal pathogens.

## Key facts

- **NIH application ID:** 9928005
- **Project number:** 5R21AI146957-02
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ILIYAN Dimitrov ILIEV
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $211,875
- **Award type:** 5
- **Project period:** 2019-05-10 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9928005

## Citation

> US National Institutes of Health, RePORTER application 9928005, Investigation of commensal bacteria-produced metabolites with activity towards mycobiota. (5R21AI146957-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9928005. Licensed CC0.

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