Urobiota analysis and genome-wide association study in pediatric recurrent urinary tract infections and vesicoureteral reflux

Urinary tract infections (UTIs) are the most common severe bacterial infections in young children, often associated with vesicoureteral reflux (VUR). To explore host genetic-microbiota interactions and their clinical implications, we analyzed the urinary microbiota (urobiota) and conducted genome-wide association studies for bacterial abundance traits in pediatric patients with UTI and VUR from the Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation cohorts. We identified 4 urobiota community types based on relative abundance, characterized by the genera Enterococcus, Prevotella, Pseudomonas, and Escherichia/Shigella, and their associations with VUR, age, and toilet training. Children with VUR exhibited decreased microbial diversity and increased abundance of genera that included opportunistic pathogens, suggesting a disrupted urobiota. We detected genome-wide significant genetic associations with urinary bacterial relative abundances, in or near candidate genes including CXCL12, ABCC1, and ROBO1, which are implicated in urinary tract development and response to infection. We showed that Cxcl12 was induced 12 hours after uropathogenic bacterial infection in mouse bladder. The association with CXCL12 suggests a genetic link between UTI, VUR, and cardiovascular phenotypes later in life. These findings provide the first characterization to our knowledge of host genetic influences on the pediatric urobiota in UTI and VUR, offering insights into the interplay between disease, host genetics, and the urobiota composition.

Authors

Institutions

Publication Details

Journal
JCI Insight
Published
2025-12-09
DOI
https://doi.org/10.1172/jci.insight.199689
Primary Topic
Pediatric Urology and Nephrology Studies
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Urobiota analysis and genome-wide association study in pediatric recurrent urinary tract infections and vesicoureteral reflux

Victoria Kolupaeva, Heekuk Park, Atlas Khan, Simone Sanna‐Cherchi et al.
JCI Insight
Pediatric Urology and Nephrology Studies
article

Urobiota analysis and genome-wide association study in pediatric recurrent urinary tract infections and vesicoureteral reflux

Victoria Kolupaeva, Heekuk Park, Atlas Khan, Simone Sanna‐Cherchi, Miguel Verbitsky, Katherine Xu, Tze Yin Lim, Iman Ghavami, P.K. Khosla, Krzysztof Kiryluk, Jeremiah Martino, Jonathan M. Barasch, Yask Gupta, Nita A. Limdi, Ali G. Gharavi, Cathy Mendelsohn, Håkon Håkonarson, Priya Krithivasan, Anne‐Catrin Uhlemann, Tanya Sezin, Daniel L. Bivona, Yuan Luo, Tian Shen, Aryan S. Ghotra
article en

Abstract

Urinary tract infections (UTIs) are the most common severe bacterial infections in young children, often associated with vesicoureteral reflux (VUR). To explore host genetic-microbiota interactions and their clinical implications, we analyzed the urinary microbiota (urobiota) and conducted genome-wide association studies for bacterial abundance traits in pediatric patients with UTI and VUR from the Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation cohorts. We identified 4 urobiota community types based on relative abundance, characterized by the genera Enterococcus, Prevotella, Pseudomonas, and Escherichia/Shigella, and their associations with VUR, age, and toilet training. Children with VUR exhibited decreased microbial diversity and increased abundance of genera that included opportunistic pathogens, suggesting a disrupted urobiota. We detected genome-wide significant genetic associations with urinary bacterial relative abundances, in or near candidate genes including CXCL12, ABCC1, and ROBO1, which are implicated in urinary tract development and response to infection. We showed that Cxcl12 was induced 12 hours after uropathogenic bacterial infection in mouse bladder. The association with CXCL12 suggests a genetic link between UTI, VUR, and cardiovascular phenotypes later in life. These findings provide the first characterization to our knowledge of host genetic influences on the pediatric urobiota in UTI and VUR, offering insights into the interplay between disease, host genetics, and the urobiota composition.

JCI InsightVol. 11(2)
Northwestern University (US), Children's Hospital of Philadelphia (US), Columbia University Irving Medical Center (US), University of Alabama at Birmingham (US), Office of Infectious Diseases (US), Precision for Medicine (United States) (US), Columbia University (US)
National Institutes of Health, NIH Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases
Openalex Percentile: Top 51%
Pediatric Urology and Nephrology Studies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.