# Defining omic-signatures in recurrent Clostridium difficile infection

> **NIH VA I01** · VETERANS HEALTH ADMINISTRATION · 2021 · —

## Abstract

ABSTRACT
Clostridium difficile infection (CDI) is one of the most prevalent and devastating healthcare-associated
infections. Following standard antibiotic therapy, up to 25% of individuals with CDI develop one or more
recurrences. Persistent or repeated episodes are difficult to treat and are a significant hardship for patients.
The high success rate of fecal microbiota transplant for recurrent CDI provides powerful insight into the
importance of restoring normal gut microbiota. However, to date, there are no microbiological or “omic”
(microbiomic, metagenomic, metabolomic) predictors of C. difficile recurrence. The objective of this proposal is
to determine temporal dynamics of microbial profiles and “omic” signatures associated with C. difficile
recurrence. Our hypothesis is that patients who do not develop a C. difficile recurrence share an identifiable set
of microbes, genes, and fecal metabolites in the gut microbiota. The rationale is that once the temporal
dynamics of microbial and “omic” signatures associated with C. difficile recurrence are well defined, candidate
microbial or “omic” biomarkers can be validated prospectively, ultimately allowing the development of
strategies to prevent recurrent CDI. Specific preemptive therapy (e.g. microbiome manipulation) may then be
developed on the basis of microbial compositions, genes, or metabolites of that microbiota. This novel
approach offers an innovative method for preventing recurrent CDI. We will test the hypothesis by pursuing the
following Specific Aims: 1) Determine the composition and structure of gut microbiota longitudinally in subjects
following CDI, 2) Determine the metagenome of C. difficile gut microbiota, and 3) Perform global metabolomic
analyses using LC-HRMS and GC-MS, including cholesterol and bile acid metabolites, to determine key
metabolites in C. difficile gut microbiota. The approach is innovative because it will utilize a combination of
unbiased, culture-independent 16S rRNA deep sequencing, metagenomic, and metabolomic approach and
innovative computational techniques and multivariate statistical methods to identify “omic” signatures in gut
microbiota associated with C. difficile recurrence. The proposed research is significant because there are
virtually no data on the relationship between gut microbiota, omic signatures and C. difficile recurrence. This
proposal will define “omic” signatures that can be validated in future studies, ultimately leading to novel
strategies based on “omic” profiles for primary prevention of recurrent CDI.

## Key facts

- **NIH application ID:** 10060735
- **Project number:** 5I01CX001391-04
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** GARY P. WANG
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2017-09-30 → 2023-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10060735

## Citation

> US National Institutes of Health, RePORTER application 10060735, Defining omic-signatures in recurrent Clostridium difficile infection (5I01CX001391-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10060735. Licensed CC0.

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