Abstract
The pediatric urinary microbiome (urobiome) has been studied in the context of healthy children and children with genitourinary pathologies including neuropathic bladder, urinary tract infection (UTI) and nephrolithiasis. Little is known about the urobiome of children with bladder and bowel dysfunction (BBD), a condition that is an established risk factor of UTI. We hypothesized that the symptoms of a child with BBD may be related to urobiome composition. To evaluate the urogenital urobiome's role in BBD, we compared the urogenital urobiomes of children with and without BBD. We performed a prospective case-control pilot study at a single large, academic children's hospital. Cases included toilet trained prepubertal females over 2 years of age with BBD established through a validated scoring system and controls included asymptomatic, presumably healthy, children. Children were excluded if they had symptoms or lab work consistent with a concurrent UTI or antibiotic course for any reason within the prior 14 days. We performed 16S ribosomal RNA gene sequencing and expanded quantitative urine culture on clean catch urine samples. To compare within sample (alpha) diversity, we used the Kruskal-Wallis test. To compare between sample (beta) diversity, we calculated the Bray-Curtis distance and performed the PERMANOVA test. Data from 25 children with BBD and 8 asymptomatic controls were analyzed. The demographic and clinical characteristics of the two comparison groups were similar, though a higher proportion of Black children were included in the asymptomatic control group. Neither alpha diversity nor beta diversity was significantly different between the two groups. The core microbiome of the BBD group included all the genera in the core urogenital urobiome of the controls, plus additional genera associated with opportunistic infection and/or UTI, including Escherichia, Campylobacter and Streptococcus. The results of both the 16S sequencing and expanded quantitative urine culture in this small study suggest that the urogenital urobiomes of children with BBD do not differ significantly from those of asymptomatic children. However, the core urogenital urobiome of children with BBD included genera associated with opportunistic infection and/or UTI. This study was limited by the sample collection method ("clean catch" midstream voided urine samples, which introduce the possibility of vulvovaginal contamination), small sample size, and unequal balance of patient characteristics between the two study groups. The urogenital urobiomes of children with and without BBD do not appear to significantly differ. Larger studies are needed to confirm these findings.
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