Background: Individuals with spina bifida (SB) have increased risk for urinary tract infection (UTI). Distinguishing UTI from asymptomatic bacteriuria is challenging in SB, often leading to overtreatment with antibiotics. Improving care for UTIs in SB patients requires a better understanding of their urinary and intestinal microbiomes. The objective of this study was to understand the diversity and composition of the urinary and intestinal microbiomes in patients with SB and evaluate how these microbiomes and resident uropathogens evolve over time. Our hypothesis was that the microbiomes of SB patients will differ in both diversity and composition from previously published studies in healthy children and that alterations in these microbiomes will influence UTI risk.
Methods: We performed a prospective, single-center study of individuals aged 0-30 with a diagnosis of SB between 10/2023 to 05/2024. Subjects were recruited in our SB clinic or in the neonatal intensive care unit after birth. Catheterized urine and stool samples were obtained during urodynamics. Skin swabs of the hand were obtained from subjects performing clean intermittent catheterization (CIC). Expanded quantitative urine culture (EQUC) and 16s RNA amplicon sequencing were performed on urine, stool, and skin specimens. Demographic and clinical data were obtained. Descriptive analyses of the clinical and EQUC data were performed. Sequencing reads were processed by DADA2 workflows, bioinformatically decontaminated using the R package Decontam, and visualized with phyloseq tools.
Results: Sixty subjects met inclusion criteria with a mean age of 7 (range 0-20) years old. Thirty-four (57%) subjects were male and 53 (88%) were white. Thirty-eight (63%) subjects had any history of UTI. Additional demographic and clinical data can be seen in Table 1. Overall, 49/60 (82%) urine specimens displayed bacterial growth on EQUC. 16s rRNA sequencing data was available from 28 subjects. Bacterial DNA was detectable (>500 16S rRNA reads) in 28/30 (97%) urine specimens and 28/28 (100%) stool samples. Escherichia-Shigella spp. were present in 20/30 (67%) of urine specimens and was the dominant genera in 50% as seen in Figure 1. Subjects with a history of prior UTI had greater abundance of Escherichia in the stool than those without a history of UTI (p < 0.05). Subjects on CIC had greater abundance of Staphylococcus spp. relative to those not on CIC (p < 0.05). Conclusions: Eighty-two percent of individuals with spina bifida had growth on EQUC and 97% had detectable bacterial DNA in the urine by amplicon sequencing, which are significantly higher than published studies analyzing catheterized urine specimens from healthy children (60% on EQUC and 84% on 16s rRNA). Escherichia is abundant within the urine of individuals with SB (67%) and significantly more abundant in the stool of individuals with prior UTI.