Kudos to Maryellen Kelly, assistant professor, and Tatyana Sysoeva (Univ. of Alabama, Huntsville) for the submission of their Multi-PI, Collaborating for the Advancement of Interdisciplinary Research in Benign Urology (CAIRIBU) application to the University of Wisconsin-Madison entitled: “Urinary Microbiome in Children with Recurrent Urinary Tract Infections." This proposal requests funding for a one-year period with a start date of July 1, 2021.

Urinary tract infections (UTI) in children have a recurrence rate of up to 50% with girls being the most affected after the first year of life. While even a single UTI can lead to renal scarring, recurrent UTI (rUTI) in children result in life-long health consequences that include increased risks of hypertension, renal insufficiency, and pregnancy complications, such as preeclampsia and preterm birth. Pediatric rUTI differ from those in adults, but the majority are still caused by uropathogenic enteric bacteria that increasingly become antibiotic resistant and harder to treat. Several studies in adults report associations between rUTI and the composition of the microbial community inhabiting the lower urinary tract - the urinary microbiome. However, there is a critical gap in knowledge surrounding the composition and development of the urinary microbiome in children and its relation to childhood rUTI. Based on the observed associations of the adult urinary microbiome with rUTI and the findings that children do have a detectable urinary microbiome, our central hypothesis is that the urinary microbiome in children with rUTI differs from that of children without rUTI. Our long-term goal is to develop a non-invasive clinical urine test that can predict children at increased risk for rUTI, and to develop a non-antibiotic intervention strategy for reducing rUTI in the identified at-risk population. To move toward this goal, we propose this pilot study that has the overall objective of determining efficient methods of characterizing the urinary microbiome in children and applying these methods to conduct a feasibility analysis in small cohorts of children with and without rUTI.

Specific Aim 1: Evaluate microbiome presence and composition in catheterized urine of children with species-level resolution.

Our working hypothesis is that there is a urinary microbiome in young children. We will test the feasibility of a novel sequencing approach to establish the species-level composition of the urinary microbiome of children. We will use our previously collected catheterized urine samples from children (n=50) who underwent voiding cystourethrograms and apply synthetic long read sequencing with positive and negative controls to obtain compositional data for bacteria in these samples.

Specific Aim 2: Compare the urinary microbiome in pilot cohorts of children with and without rUTI.

Our working hypothesis is that there will be significant changes in the urinary microbiome in children with rUTI. We will collect demographic and clinical variables along with voided urine samples in children with (n=20) and without rUTI (n=20) to compare the compositional profile of the microbial communities present in each phenotype. Voided urine samples are expected to contain microbes from several adjacent niches (i.e. bladder, skin, genitals), and thus have a broader representation of microbes that are known to affect bladder colonization with/by commensal or pathogenic bacteria and provide relevant information from the most clinically available samples.