Distinguishing Features of the Urinary Bacterial Microbiome in Patients with Neurogenic Lower Urinary Tract Dysfunction

Abstract

Purpose: We aimed to characterize the urinary microbiome of catheterizing patients with neurogenic lower urinary tract dysfunction (NLUTD) and to evaluate differences based on type of bladder management or frequency of urinary tract infections.

Materials and methods: This is a prospective, cross-sectional study of urine samples from asymptomatic, catheterizing patients with neurogenic lower urinary tract dysfunction who used either clean intermittent catheterization or indwelling catheters. Patients without symptoms of urinary tract infection provided a catheterized urine sample for urinalysis, culture and bacterial community microbiome analysis.

Results: A total of 95 patients submitted urine for analysis, of whom 69 had sufficient sequence reads (>1,203) for microbiome analysis. Cases with low bacterial signal amplification were associated with use of vaginal estrogen, no intradetrusor botulinum toxin A use and no growth on standard urine culture. The most abundant operational taxonomic units were from the phylum Proteobacteria, classified as Enterobacteriaceae and Escherichia. Alpha diversity varied among those who used indwelling catheters vs clean intermittent catheterization, and those who underwent botulinum toxin A injection vs not. On linear discriminate analysis, the relative abundance of the operational taxonomic units identified as Pseudomonas was higher among patients using indwelling catheters relative to clean intermittent catheterization. The operational taxonomic unit identified as Aerococcus was at a higher relative abundance among males compared to females.

Conclusions: Enterobacteriaceae and Escherichia were the most abundant genera in the urinary microbiome of patients with neurogenic lower urinary tract dysfunction. Urinary microbiome diversity varied based on bladder management type. Future clinical correlations between microbiome of neurogenic patients and clinical presentation may help guide treatment strategies.

Keywords: botulinum toxins; microbiota; neurogenic; type A; urinary bladder; urinary tract infections; urine.

Figure 1:

Stacked bar graph of the 15 most abundant genera among patients with neurogenic bladder. Each bar represents a different patient sample.

Figure 2:

Box plot of diversity within samples (alpha diversity) of patients with neurogenic lower urinary tract dysfunction using (A) intermittent (CIC) versus indwelling catheter and use of intradetrusor (B) onabotulinumtoxin A (BTX-A) injection. Inverse Simpson Index of zero indicates no diversity and greater Inverse Simpson Index indicates greater diversity within each sample.

Figure 3:

Box plot of Linear discriminant analysis (LDA) effect size (LEfSe) demonstrating that while overall relative abundance is low (A) Pseudomonas is differentially abundant among individuals utilizing indwelling catheters versus those on CIC, and (B) Aerococcus is differentially abundant among males compared to females.