PROJECT SUMMARY
Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated diarrhea in the United
States, causing 12,900 deaths in 2017. CDI has demonstrated a rapid increase in incidence in the last two
decades, with rate increases most pronounced in pediatric patients with inflammatory bowel disease (IBD).
IBD, a chronic disease characterized by inflammation of the gastrointestinal tract, has also demonstrated
increasing incidence in children worldwide and is considered a globally important pediatric disease. The co-
occurrence of IBD and CDI is associated with worse outcomes including longer hospital stays, higher charges,
and greater need for blood transfusions. Conversely, children with IBD also have high rates of C. difficile
colonization, defined as the presence of C. difficile in the absence of symptoms attributable to C. difficile.
Symptoms of CDI in IBD patients are indistinguishable from symptoms of an IBD flare in patients with C.
difficile colonization. Microbial perturbations, biomolecules associated with germination and metabolism, and
antitoxin antibodies have been studied individually for their influence on colonization and CDI but primarily in
cross-sectional approaches and not applied to children with IBD.
The research detailed in this proposal responds directly to the need to better understand the
determinants and sequalae of CDI and C. difficile colonization in pediatric patients with IBD and includes the
following specific aims: 1) To investigate the role of germination and metabolic mediators as they relate to the
development of, and recovery from, C. difficile colonization, symptomatic CDI, and IBD flares. 2) To examine
differences in the intestinal microbiome that are predictive of C. difficile colonization, disease, and recovery in
children with IBD. 3) To determine the prevalence and impact of C. difficile antitoxin antibodies in children with
IBD.
For the past 8 years the candidate has worked closely with her mentor, Dr. Kathryn Edwards on a
variety of CDI-related projects which have included the prospective enrollment of over 360 pediatric patients.
Through this project, the candidate plans to longitudinally follow children with IBD with serial sampling of stool
and serum to better understand the interaction of CDI and IBD. The overarching objective of this mentored
career development experience is for the candidate to emerge as an independent clinical investigator of C.
difficile and IBD, become established in metabolite determination and microbiome analysis, and serve as an
interface between clinical research and laboratory sciences through carefully planned translational
approaches. To accomplish this goal, the candidate will augment her prior training with advanced coursework
in microbiome analysis, clinical research, and leadership training. Throughout the award period, the candidate
will work closely with a multidisciplinary team of mentors including experts in infectious diseases, IBD,
biostatistics, microbiome analysis, and molecular techniques to carry out her stated aims and career goals.
