# Orally active metabolite therapy against C. difficile infection

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $234,000

## Abstract

Project Summary
C. difficile infection is an extremely debilitating disease with high mortality rates and expensive medical care
costs. Current antibiotic therapies such as vancomycin and metronidazole leave patients prone to relapse;
therefore, more effective therapeutic approaches are actively sought after. A recently published report from our
laboratory demonstrated that a cathelicidin mimic compound CSA13 could inhibit C. difficile primary infection
and vancomycin-associated relapse in mice. We found that the oral administration of CSA13 modulated the
intestinal microbiome in C. difficile-infected mice. Metabolomic analysis revealed a specific pattern of fecal
metabolites associated with the therapeutic effect of CSA13. Oral administration of four metabolites mimicked
the protective effect of CSA13. Metabolite treatment, like CSA13 treatment, prevented vancomycin-associated
relapse of C. difficile-infected mice. Metabolites may be a potential therapeutic agent against primary C. difficile
infection and preventing C. difficile relapse. However, it is necessary to optimize the regimen for maximal
efficacy and characterize its impact on C. difficile pathophysiology, intestinal microbiome, and host immune
responses. This application proposes to determine (1) whether the metabolites inhibit C. difficile toxin
production and spore generation; (2) whether metabolites exert a cytoprotective effect in epithelial cells and
suppress toxin-mediated immune responses. We will optimize the dosing regimen of mixed metabolites for
maximal protection against CDI. The overall impact of this study will discover a novel way of treating CDI.
Specific protective metabolite therapy is safer, more convenient, and more straightforward than fecal
microbiota transplantation.

## Key facts

- **NIH application ID:** 9836617
- **Project number:** 5R21AI137663-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Hon Wai Koon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $234,000
- **Award type:** 5
- **Project period:** 2018-12-14 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836617

## Citation

> US National Institutes of Health, RePORTER application 9836617, Orally active metabolite therapy against C. difficile infection (5R21AI137663-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9836617. Licensed CC0.

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