# Bile Acids and Clostridium scindens Inhibit C. difficile: Role of Secreted Antibacterial Compounds

> **NIH VA I01** · VA VETERANS ADMINISTRATION HOSPITAL · 2020 · —

## Abstract

ABSTRACT
PI- Phillip B. Hylemon, Ph.D.
Title: “Bile Acids and Clostridium scindens Inhibit C. difficile: Role of Secreted Antibacterial
Compounds”
 Clostridium difficile, the cause of antibiotic associated diarrhea and colitis, is a growing
health threat for patients taking broad spectrum antibiotics. It has been estimated that C. difficile
may be responsible for almost a half a million infections per year and 29,000 deaths in the US at
an annual cost of $4.8 billion dollars. Patients on broad-spectrum antibiotics markedly decrease
the levels of protective gut microbiota and allows proliferation of C. difficile normally found in low
levels in some individuals. Patients treated with antibiotics, especially in hospitals, are also at
risk for colonization by C. difficile spores, which germinate in the GI tract (stimulated by specific
bile acids) producing vegetative cells that secrete toxins A and B causing diarrhea and colitis.
Patients with antibiotics associated diarrhea and/or colitis are routinely treated with either
metronidazole or vancomycin to kill C. difficile vegetative cells colonizing the colon; however, up
to 30% all patients successfully treated with these antibiotics will relapse following cessation of
antibiotic therapy. Fecal transplants, using gut microbiota from healthy donors, have been highly
successful in treating relapsing patients. Recent studies, published in Nature, were undertaken to
determine which members of the gut microbiota are responsible for resistance to C. difficile
infection. It was reported that Clostridium scindens, a human gut bacterium that converts the
primary bile acids, cholic acid (CA) and chenodeoxycholic acid (CDCA) to secondary bile acids,
deoxycholic acid (DCA) and lithocholic acid (LCA), respectively, is strongly associated with
inhibition of C. difficile infections in both animal models and in human patients. This past year, our
laboratory made two important discoveries that may explain how C. difficile is able to colonize the
human GI tract, when patients are treated with antibiotics, and how C. scindens inhibits the growth
and colonization by C. difficile. Aim 1: Confirm the structure and characterize the mechanism of
action of a cyclic 6 amino acid antibiotic peptide secreted by C. difficile that inhibits the growth of
C. scindens and other human gut bacteria. Subaim 1a. Determine if clinical strains of C. difficile
secrete the same compound. Aim 2: Purify, characterize, and determine the structure of a CA
inducible antibacterial compound(s) secreted by C. scindens ATCC 35704 and VPI 12708 that
inhibits the growth of C. difficile and other pathogenic bacteria in vitro. Subaim 2a. Determine the
spectrum of different bacteria inhibited by this compound(s). Subaim 2b. Identify the bile acid
inducible genes encoding the enzymes(s) involved in the synthesis of this antibacterial compound
using RNAseq technology. Subaim 2c. Characterize the mechanism of inhibition of C. difficile
growth by this compou...

## Key facts

- **NIH application ID:** 9859298
- **Project number:** 5I01BX001328-08
- **Recipient organization:** VA VETERANS ADMINISTRATION HOSPITAL
- **Principal Investigator:** PHILLIP B HYLEMON
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2020
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2012-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9859298

## Citation

> US National Institutes of Health, RePORTER application 9859298, Bile Acids and Clostridium scindens Inhibit C. difficile: Role of Secreted Antibacterial Compounds (5I01BX001328-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9859298. Licensed CC0.

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