Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence

Abstract

Background: Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described.

Objective: We sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery.

Study design: Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models.

Results: The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P < .001). No associations were detected with stress urinary incontinence symptoms. Increased diversity was also associated with a concomitant lower frequency of Lactobacillus in hormone-negative women.

Conclusion: Women undergoing stress urinary incontinence surgery have detectable urinary microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms.

Keywords: bladder; estrogen; microbiome; stress urinary incontinence; urgency urinary incontinence.

Conflict of interest statement

The following authors report no disclosures: Thomas-White, Kliethermes, Moalli, Norton, Richter, Zimmern, Kusek. The following authors report disclosures: E. Lukacz: Uroplasty (grant), Pfizer (research support), Up to Date (author royalties) L. Rickey: Analytica (consultant), Health Monitor Netowrk (consultant), Up to Date (author royalties), H. Richter: Kimberly Clark (consultant), UpToDate (royalties) Wolfe: Astellas Scientific and Medical Affairs (research support) Brubaker: Up to Date (editorial royalties)

Published by Elsevier Inc.

Figures

Figure 1. Using phylogenetic similarity to determine similar profiles (aka urotypes)

For each taxonomic level (Phylum, Class, Order, Family, Genus), all samples were compared to each other using Bray-Curtis similarity, which produces a phylogenetic tree, or dendrogram, in which shorter branches link similar samples, and longer branches link more dissimilar samples. Therefore, each tree can be divided into groups or clades. When aligned to relative sequencing abundance, the clades of each tree separate by the identity of the predominant organism. Below is one example, the genus classification from the first replica. The urotype indicates the clades that fall into the same urotype. Each urotype is named for the predominant genus. If no one genus is predominant, then the urotype is considered non-predominant. All corresponding graphs for each replica and each taxonomic level can be found in supplementary Figure S1. Genus Identification from the first sequencing replica set

Figure 2. Phylogenetic diversity and urotype distribution between estrogen status

Relative abundance of the microbial community at the genus level for each of the 4 estrogen groups. Each bar is a separate individual with the percent of total classified reads to the genus level represented on the y-axis. Phylogenetic relatedness as measured by Bray-Curtis dissimilarity is depicted in the dendrograms above each group. The full cohort is separated by hormone status: pre-menopausal, post-menopausal (with or without self-reported, current exogenous hormones) or uncertain about hormonal status. Estrogen positive groups (pre-menopausal and those currently on exogenous estrogen) have a greater prevalence of Lactobacillus-predominant individuals (blue) than the estrogen negative group. The estrogen negative group has a greater number of non-predominant (multi-colored) profiles compared to the estrogen positive populations.