# Effect of bile salt hydrolase inhibitors on Clostridium difficile infection

> **NIH NIH R21** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2022 · $184,250

## Abstract

Project Summary
 Clostridium difficile infection (CDI) is the major cause of nosocomial diarrhea with increasing
incidence rates worldwide. Germination of spores, mediated by sensing specific cues in the gut (named
germinants), is an essential early requirement for the pathogenesis of C. difficile and CDI development.
Bile acids (BAs) have been recognized as the major group of germinants in the intestine. However, it is
still unknown which and how specific intestinal BA signature influence in vivo C. difficile germination and
CDI development, primarily due to lack of appropriate tools for animal study in a controlled system. The
bacterial bile salt hydrolase (BSH) is a gateway enzyme significantly influencing BA metabolism and BA
profile in the intestine. Recently, we have discovered and validated three potent and broad-spectrum
BSH inhibitors using both in vitro and in vivo systems, which provides us an excellent tool to examine C.
difficile germination in response to intestinal BAs for CDI development. We hypothesize that oral
administration of the BSH inhibitors would alter BA profile in the intestine, consequently affecting the
development and severity of CDI. To test this, we plan to evaluate the effects of the BSH inhibitors on
CDI in a mouse model. We will comprehensively examine which and how specific intestinal BA signatures
influence in vivo C. difficile germination, cell growth, and toxin production for CDI development. Through
a powerful combination of metabolomics, genomics, molecular, microbiological, and transcriptomics
approaches in conjunction with a well-established mouse model, we expect this project will fill a significant
knowledge gap in C. difficile pathogenesis, and provide insights into the development of effective
strategies to prevent and control CDI.

## Key facts

- **NIH application ID:** 10495265
- **Project number:** 5R21AI159745-02
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** JUN LIN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $184,250
- **Award type:** 5
- **Project period:** 2021-09-24 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495265

## Citation

> US National Institutes of Health, RePORTER application 10495265, Effect of bile salt hydrolase inhibitors on Clostridium difficile infection (5R21AI159745-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10495265. Licensed CC0.

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