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. 2016 Jul 27;6:78.
doi: 10.3389/fcimb.2016.00078. eCollection 2016.

Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?

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Free PMC article

Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity?

Lisa Karstens et al. Front Cell Infect Microbiol. .
Free PMC article

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.

Keywords: bladder disease; bladder microbiome; human microbiome; overactive bladder; urge; urinary incontinence; urinary microbiome.

Figures

Figure 1
Figure 1
Distribution of bacteria in urine samples in control and UUI groups. (A) The log transformed concentrations of bacteria. (B) The number of reads per sample after preprocessing. These reads were classified into operational taxonomic units (C) and further classified into bacterial genera (D). OTUs, operations taxonomic units; CTL, control; UUI, urgency urinary incontinence.
Figure 2
Figure 2
Microbiome diversity overview between women with normal bladder function (CTL, controls) and women with daily urgency urinary incontinence (UUI, cases). At the phyla level (inner circle), the composition is similar with a few slight differences. At the family level (outer circle), however, some differences are apparent such as a marked decrease in Bifodobacteriaceae and Prevotellaceae, and increase in Enterobacteriaceae and Flavobacteriaceae in UUI compared to controls.
Figure 3
Figure 3
A Venn diagram depicting the number of bacterial families (A) and genera (B) that are shared and unique between CTL and UUI urine.
Figure 4
Figure 4
Differentially abundant bacteria in women with UUI relative to controls. Many of these bacteria were identified at the genus level. Nine bacteria were increased and five were decreased in women with UUI compared to controls. Of the increased bacteria, five have previously been implicated in UTI (highlighted in bold font). *FDR adjusted p < 0.1, **FDR-adjusted p < 0.05.
Figure 5
Figure 5
Clustering of participants based on urinary microbiome profiles. The dendrogram (upper) is based on hierarchical clustering of the weighted Unifrac distances between the bacteria found in urine samples from controls (C) and women with UUI (U). The dashed line indicates where the clades were divided into three clusters: Cluster 1 which is comprised of five controls and three cases; Cluster 2 which is predominantly cases (six cases, one control), and Cluster 3 which is only controls. The sample type is indicated by the rectangle below the cluster bar: U, case; C, control. One case sample did not fall into a cluster at this level. The stacked bar plots below the heatmap represent the relative abundance of the bacterial families identified by 16S sequences present in each urine specimen. Bacterial families with an overall mean abundance < 0.5%, are grouped as “Other.” The main color is indicative of the bacterial phyla with the shade indicative of bacteria family.
Figure 6
Figure 6
Increasing UUI symptom severity is associated with decreased microbial diversity in women with UUI. We identified relationships between the richness and evenness of the urinary microbiome (as measured by the Inverse Simpson and Shannon indices, where lower scores are indicative of lower microbial diversity) and UUI symptom severity. The percent of incontinent episodes is measured by percent of voids with an USS score equal to 4 on a 3 day bladder dairy, and an increase indicates more incontinent episodes. The urogenital distress inventory is a validated questionnaire measuring symptom distress from incontinence and a higher score indicates more distress. Both of these measures have a significant negative correlation with microbial diversity. The OABq-symptom bother is the health related quality of life score from the validated overactive bladder questionnaire. A higher score indicates less symptom bother and is positively correlated with diversity measures. Together, these data indicate that a reduction in microbial diversity is associated with an increase in symptom severity.

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