The association between the urine microbiome, the host immune response and urinary symptoms in children with spina bifida

Catherine Forster, MD, MS is a pediatrician in hospital medicine whose overarching career goal is to be a world-recognized leader on UTIs in children with neuropathic bladder. Research: Despite the importance of urinary tract infections (UTIs) to health outcomes in children with neuropathic bladders, there are currently no methods to accurately diagnose UTIs in this population. This

proposal will begin to fill that gap. The goals of this proposal are to identify children who should be tested for a UTI, develop a highly specific diagnostic method for UTI using mouse models, and translate these results into a pilot cohort of children. These goals will be attained through completion of the following specific aims: 1)

Develop an algorithm based on clinical characteristics to determine the probability of UTI in children with spina bifida; 2) Identify the relationship between urine microbial diversity and urinary biomarkers in mouse models of neuropathic bladder; and 3) Explore the association between UTI and urobiome diversity and/or urine

biomarkers in children with spina bifida. Aim 1 will be completed through use of data from the multi-institutional Urologic Management to Preserve Initial Renal Function Protocol for Young Children with Spina Bifida study. Aim 2 will use both genetic and surgical mouse models of neuropathic bladder. In Aim 3, the urobiome and

urine biomarkers will be measured in symptomatic children with spina bifida. Career Development: Together with her mentors, Dr. Carl Bates and Dr. Nader Shaikh, Dr. Forster has created a career development plan built upon her prior training that is designed to address the areas where she requires additional training: Gain additional knowledge around mouse bladder studies and genetic models

of bladder disease, create and maintain a mouse colony, gain experience with interpretation of urodynamic data, develop working knowledge of bioinformatic approaches to analyze 16S rRNA sequencing data, and develop expertise with recruiting and collecting prospective urine samples from a cohort of pediatric patients.

The proposed training plan will provide Dr. Forster with the necessary skills to validate the results of this work. Environment: This research will take place within the Children’s Hospital of Pittsburgh (CHP). The proposed career development plan utilizes the intellectual resources available through the University of Pittsburgh and

CHP, including the Center for Microbiome and Medicine, and nationally recognized seminars and courses. Summary: This proposed innovative research will expand the evidence base for the diagnosis of UTI in children with spina bifida. Aligned with NIDDK’s mission, this work will be an important contribution to

improving the health of children with neuropathic bladders. Dr. Forster's research and clinical training, prior research experiences, and dedicated mentorship team make her ideally suited to pursue this research. This award will facilitate Dr. Forster’s continued development into an independent investigator in the conduct of

research of the optimizing the care and outcomes of children with neuropathic bladders.