Abstract

Objectives: Traditionally, the urinary tract has been thought to be sterile in the absence of a clinically identifiable infection. However, recent evidence suggests that the urinary tract harbors a variety of bacterial species, known collectively as the urinary microbiome, even when clinical cultures are negative. Whether these bacteria promote urinary health or contribute to urinary tract disease remains unknown. Emerging evidence indicates that a shift in the urinary microbiome may play an important role in urgency urinary incontinence (UUI). The goal of this prospective pilot study was to determine how the urinary microbiome is different between women with and without UUI. We also sought to identify if characteristics of the urinary microbiome are associated with UUI severity.Methods: We collected urine from clinically well-characterized women with UUI (n = 10) and normal bladder function (n = 10) using a transurethral catheter to avoid bacterial contamination from external tissue. To characterize the resident microbial community, we amplified the bacterial 16S rRNA gene by PCR and performed sequencing using Illumina MiSeq. Sequences were processed using the workflow package QIIME. We identified bacteria that had differential relative abundance between UUI and controls using DESeq2 to fit generalized linear models based on the negative binomial distribution. We also identified relationships between the diversity of the urinary microbiome and severity of UUI symptoms with Pearson's correlation coefficient.Results: We successfully extracted and sequenced bacterial DNA from 95% of the urine samples and identified that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI. We found the relative abundance of 14 bacteria significantly differed between control and UUI samples. Furthermore, we established that an increase in UUI symptom severity is associated with a decrease in microbial diversity in women with UUI.Conclusions: Our study provides further characterization of the urinary microbiome in both healthy controls and extensively phenotyped women with UUI. Our results also suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of microbial diversity may be associated with clinical severity.

Highlights

  • 19% of women over the age of 44 suffer from Urgency Urinary Incontinence (UUI; Stewart et al, 2003)—a strong sensation of the need to urinate (“urgency”) followed by immediate leakage of a large volume of urine

  • Our results indicate that there is a polymicrobial community in the female bladder in both healthy controls and women with UUI

  • These results suggest that the urinary microbiome may play an important role in the pathophysiology of UUI and that the loss of diversity may be associated with clinical severity

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Summary

Introduction

19% of women over the age of 44 suffer from Urgency Urinary Incontinence (UUI; Stewart et al, 2003)—a strong sensation of the need to urinate (“urgency”) followed by immediate leakage of a large volume of urine. DO is only observed in approximately 58% of women with UUI (Hashim and Abrams, 2006) and treatments aimed at reducing DO are ineffective for approximately half of the people that use them (Nitti et al, 2010). Even in those with DO, it is unclear what underlying factors contribute to this urodynamic observation. These findings suggest that more attention needs to be placed on understanding pathophysiologic mechanisms that contribute to UUI. Understanding these mechanisms is a necessary step toward improving effectiveness of existing therapy and introducing new therapeutic approaches

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