# Understanding Clostridium difficile Infection in Patients with inflammatory Bowel Disease

> **NIH NIH K23** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $196,358

## Abstract

PROJECT SUMMARY
Over the last decade the incidence and severity of Clostridium difficile infection (CDI) has increased, and these
infections have had a particularly deleterious effect on patients with inflammatory bowel disease (IBD) by
eliciting disease flares and increasing risk of colectomy. It is known that IBD patients have a 10% lifetime risk
of getting CDI and experience significantly higher rates of recurrence compared to non-IBD patients.
Mechanistically, recurrent CDI is thought in part to be due to a loss of key commensal species that provide bile
transforming activities, which convert primary bile acids, that serve as pro-germination signals to C. difficile, to
secondary bile acids which have been shown to be inhibitory to germination and to the pathogenesis of the
organism. Additionally, Fecal Microbiota Transplantation (FMT), a major treatment breakthrough for refractory
CDI, is believed to work in part by reconstituting bile salt hydrolase activity. What is not known is why patients
with IBD are at such an increased risk for recurrent CDI given that CDI studies notably lack IBD patients as this
patient population has proven challenging given many suffer from baseline diarrhea. There is an urgent need
to better risk stratify those with IBD-CDI by utilizing mechanistic risk factors in addition to traditional
epidemiologic exposures. By individualizing risk predictors, high risk patients will be identified more promptly
and offered appropriate treatments earlier, thus preventing severe complications of IBD, improving symptom
burden and quality of life. Our overall objective is to identify IBD patients at risk for recurrent CDI earlier in their
disease course and provide therapy with FMT to not only prevent recurrent CDI but also the downstream
consequences associated with CDI. Our central hypothesis is that (1) identification of clinical, microbial and
metabolic risk factors, specifically bile acid profiles, for CDI recurrence among patients with IBD who have
experienced their first episode of CDI will allow for earlier identification of high risk patients and (2) FMT
performed after an initial episode of CDI in patients with IBD will be safe and will effectively reconstitute bile
salt hydrolase activity. The rationale for the proposed research is that unlike non-IBD patients, many IBD
patients are at risk for bile acid malabsorption, either from ongoing bowel inflammation and diarrhea or prior
resections. Given that IBD-CDI patients are often excluded from trials, understanding the extent to which
alterations in bile acid composition explain the higher rates of CDI recurrence seen in this population is critical
to providing more targeted therapies. The recent expansion in microbiome research has now made it possible
to ascertain detailed gut bacterial profiles as well as their metabolites.

## Key facts

- **NIH application ID:** 10143233
- **Project number:** 5K23DK120898-02
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Jessica R. Allegretti
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $196,358
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10143233

## Citation

> US National Institutes of Health, RePORTER application 10143233, Understanding Clostridium difficile Infection in Patients with inflammatory Bowel Disease (5K23DK120898-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10143233. Licensed CC0.

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