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Urinary Tract Infections in Children with Vesicoureteral Reflux Are Accompanied by Alterations in Urinary Microbiota
Dijana Vitko1, Joseph W McQuaid2, Ali Hashemi Gheinani3
1Department of Urology, Boston Children's Hospital, Boston, MA, USA; Department of Surgery, Harvard Medical School, Boston, MA, USA.
Insights
Urinary microbiota and metabolites differ in children with vesicoureteral reflux (VUR), increasing UTI and kidney damage risk. These urinary changes may help identify at-risk patients.
Area of Science:
- Microbiology
- Metabolomics
- Pediatric Nephrology
Background:
- Vesicoureteral reflux (VUR) in children elevates risks for recurrent urinary tract infections (UTIs) and renal scarring.
- The role of urinary microbiota (uMB) and metabolic profiles in VUR pathology remains understudied.
- Gut microbiota are known to influence disease, but urinary tract-specific microbial and metabolic associations are unclear.
Purpose of the Study:
- To identify dominant urinary microbiota genera and metabolites associated with UTIs in pediatric VUR patients.
- To investigate the relationship between urinary bacterial communities, metabolic profiles, and VUR.
- To understand how UTIs remodel urinary bacterial communities in VUR.
Main Methods:
- 16S ribosomal RNA sequencing of urine samples (n=49) to analyze uMB composition.
- Metabolomic analysis using mass spectrometry (n=96) to profile urinary metabolites.
- Comparison of uMB and metabolic profiles between VUR patients and controls, and correlation with UTI status.
Main Results:
- Distinct uMB profiles were observed: Dorea- and Escherichia-dominant in VUR patients, Prevotella- and Lactobacillus-dominant in controls (p < 0.001).
- Urinary microbial composition varied significantly with recurrent febrile UTI status (p = 0.001).
- 243 altered urinary metabolites were identified in VUR patients with UTIs, impacting energy, amino acid, nucleotide, and lipid metabolism (p < 0.05).
- VUR specimens showed altered bacteria-associated metabolic pathways, including glutamate degradation, methyl-citrate cycle, and bile acid metabolism.
Conclusions:
- Significant differences exist in urinary commensal bacteria and metabolites between children with and without VUR.
- These urinary microbial and metabolic alterations may serve as biomarkers for identifying children at risk of VUR-associated kidney damage.
- The findings suggest a remodeling of urinary bacterial communities and associated metabolic pathways in response to UTIs in VUR patients.
Abstract:
Children with vesicoureteral reflux (VUR) are at an increased risk of recurrent urinary tract infections (UTIs) and renal scarring. Gut microbiota are associated with disease phenotypes, but there has been no study that associates urinary microbiota (uMB) and metabolic profiles with VUR pathology. To identify dominant uMB genera and metabolites associated with UTIs in VUR, urine samples collected under sterile conditions underwent 16S ribosomal RNA sequencing (n = 49) and metabolomic analysis by mass spectrometry (n = 96). Alterations in uMB and metabolomic profiles in VUR patients suggest remodeling of urinary bacterial communities after UTIs: Dorea- and Escherichia-dominant uMB profiles were more frequently identified in participants with VUR. Prevotella- and Lactobacillus-dominant uMB profiles were more prevalent in controls (p < 0.001). Microbial composition varied based on recurrent febrile UTI status (p = 0.001). A total of 243 urinary metabolites involved in energy, amino acid, nucleotide, and lipid metabolism were altered in VUR patients with UTIs (p < 0.05). Importantly, VUR specimens revealed changes in the bacteria-associated metabolic pathways such as glutamate degradation, methyl-citrate cycle, and bile acid metabolism. PATIENT SUMMARY: Differences in urinary commensal bacteria and metabolites exist between children with and without vesicoureteral reflux (VUR). These changes may be utilized to identify patients at risk of VUR-associated kidney damage.
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