Dataset Information

The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

ABSTRACT: Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this study, we used 16S rRNA gene sequencing to classify bacterial DNA and expanded quantitative urine culture (EQUC) techniques to isolate live bacteria in urine collected by using a transurethral catheter from women with UUI and, in comparison, a cohort without UUI. For these cohorts, we demonstrated that the UUI and non-UUI urinary microbiomes differ by group based on both sequence and culture evidences. Compared to the non-UUI microbiome, sequencing experiments revealed that the UUI microbiome was composed of increased Gardnerella and decreased Lactobacillus. Nine genera (Actinobaculum, Actinomyces, Aerococcus, Arthrobacter, Corynebacterium, Gardnerella, Oligella, Staphylococcus, and Streptococcus) were more frequently cultured from the UUI cohort. Although Lactobacillus was isolated from both cohorts, distinctions existed at the species level, with Lactobacillus gasseri detected more frequently in the UUI cohort and Lactobacillus crispatus most frequently detected in controls. Combined, these data suggest that potentially important differences exist in the urinary microbiomes of women with and without UUI, which have strong implications in prevention, diagnosis, or treatment of UUI. Importance: New evidence indicates that the human urinary tract contains microbial communities; however, the role of these communities in urinary health remains to be elucidated. Urgency urinary incontinence (UUI) is a highly prevalent yet poorly understood urinary condition characterized by urgency, frequency, and urinary incontinence. Given the significant overlap of UUI symptoms with those of urinary tract infections, it is possible that UUI may have a microbial component. We compared the urinary microbiomes of women affected by UUI to those of a comparison group without UUI, using both high-throughput sequencing and extended culture techniques. We identified statistically significant differences in the frequency and abundance of bacteria present. These differences suggest a potential role for the urinary microbiome in female urinary health.

SUBMITTER: Pearce MM

PROVIDER: S-EPMC4161260 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

Pearce Meghan M MM Hilt Evann E EE Rosenfeld Amy B AB Zilliox Michael J MJ Thomas-White Krystal K Fok Cynthia C Kliethermes Stephanie S Schreckenberger Paul C PC Brubaker Linda L Gai Xiaowu X Wolfe Alan J AJ

mBio 20140708 4

Bacterial DNA and live bacteria have been detected in human urine in the absence of clinical infection, challenging the prevailing dogma that urine is normally sterile. Urgency urinary incontinence (UUI) is a poorly understood urinary condition characterized by symptoms that overlap urinary infection, including urinary urgency and increased frequency with urinary incontinence. The recent discovery of the urinary microbiome warrants investigation into whether bacteria contribute to UUI. In this s ...[more]

PMID: 25006228

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Project description:PurposeWe characterize patients with urinary urgency with vs without urgency urinary incontinence who presented to clinics actively seeking treatment for their symptoms.Materials and methodsParticipants who enrolled in the Symptoms of Lower Urinary Tract Dysfunction Research Network were categorized into urinary urgency with vs without urgency urinary incontinence. Participants were followed for 1 year; their urinary symptoms, urological pain, psychosocial factors, bowel function, sleep disturbance, physical activity levels, physical function, and quality of life were compared. Mixed effects linear regression models were used to examine the relationships between urgency urinary incontinence and these factors.ResultsAmong 683 participants with urinary urgency at baseline, two-thirds (n=453) also had urgency urinary incontinence; one-third (n=230) had urinary urgency-only without urgency urinary incontinence. No differences were detected in urological pain between urinary urgency-only and urgency urinary incontinence. Those with urgency urinary incontinence had more severe urgency and frequency symptoms, higher depression, anxiety, perceived stress scores, more severe bowel dysfunction and sleep disturbance, lower physical activity levels, lower physical function, and worse quality of life than those with urinary urgency-only. Among those with urinary urgency-only at baseline, 40% continued to have urinary urgency-only, 15% progressed to urgency urinary incontinence, and 45% had no urgency at 12 months. Fifty-eight percent with urgency urinary incontinence at baseline continued to report urgency urinary incontinence at 12 months, while 15% improved to urinary urgency-only, and 27% had no urgency.ConclusionsPatients with urgency urinary incontinence have severe storage symptoms, more psychosocial symptoms, poorer physical functioning, and worse quality of life. Our data suggested urgency urinary incontinence may be a more severe manifestation of urinary urgency, rather than urinary urgency and urgency urinary incontinence being distinct entities.

Project description:ObjectivesTraditionally, 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.MethodsWe 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.ResultsWe 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.ConclusionsOur 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.

Project description:BackgroundAnticholinergic medications and onabotulinumtoxinA are used to treat urgency urinary incontinence, but data directly comparing the two types of therapy are needed.MethodsWe performed a double-blind, double-placebo-controlled, randomized trial involving women with idiopathic urgency urinary incontinence who had five or more episodes of urgency urinary incontinence per 3-day period, as recorded in a diary. For a 6-month period, participants were randomly assigned to daily oral anticholinergic medication (solifenacin, 5 mg initially, with possible escalation to 10 mg and, if necessary, subsequent switch to trospium XR, 60 mg) plus one intradetrusor injection of saline or one intradetrusor injection of 100 U of onabotulinumtoxinA plus daily oral placebo. The primary outcome was the reduction from baseline in mean episodes of urgency urinary incontinence per day over the 6-month period, as recorded in 3-day diaries submitted monthly. Secondary outcomes included complete resolution of urgency urinary incontinence, quality of life, use of catheters, and adverse events.ResultsOf 249 women who underwent randomization, 247 were treated, and 241 had data available for the primary outcome analyses. The mean reduction in episodes of urgency urinary incontinence per day over the course of 6 months, from a baseline average of 5.0 per day, was 3.4 in the anticholinergic group and 3.3 in the onabotulinumtoxinA group (P=0.81). Complete resolution of urgency urinary incontinence was reported by 13% and 27% of the women, respectively (P=0.003). Quality of life improved in both groups, without significant between-group differences. The anticholinergic group had a higher rate of dry mouth (46% vs. 31%, P=0.02) but lower rates of catheter use at 2 months (0% vs. 5%, P=0.01) and urinary tract infections (13% vs. 33%, P<0.001).ConclusionsOral anticholinergic therapy and onabotulinumtoxinA by injection were associated with similar reductions in the frequency of daily episodes of urgency urinary incontinence. The group receiving onabotulinumtoxinA was less likely to have dry mouth and more likely to have complete resolution of urgency urinary incontinence but had higher rates of transient urinary retention and urinary tract infections. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women's Health; ClinicalTrials.gov number, NCT01166438.).

Project description:BackgroundWomen with refractory urgency urinary incontinence (ie, unresponsive to behavioral and pharmacological interventions) are treated with onabotulinumtoxinA or sacral neuromodulation.ObjectiveThe objective of the study was to compare treatment efficacy and adverse events in women <65 and ≥65 years old treated with onabotulinumtoxinA or sacral neuromodulation.Study designThis study was a planned secondary analysis of a multicenter, randomized trial that enrolled community-dwelling women with refractory urgency urinary incontinence to onabotulinumtoxinA or sacral neuromodulation treatments. The primary outcome was a change in mean daily urgency urinary incontinence episodes on a bladder diary over 6 months. Secondary outcomes included ≥75% urgency urinary incontinence episode reduction, change in symptom severity/quality of life, treatment satisfaction, and treatment-related adverse events.ResultsBoth age groups experienced improvement in mean urgency urinary incontinence episodes per day following each treatment. There was no evidence that mean daily urgency urinary incontinence episode reduction differed between age groups for onabotulinumtoxinA (adjusted coefficient, -0.127, 95% confidence interval, -1.233 to 0.979; P = .821) or sacral neuromodulation (adjusted coefficient, -0.698, 95% confidence interval, -1.832 to 0.437; P = .227). Among those treated with onabotulinumtoxinA, women <65 years had 3.3-fold greater odds of ≥75% resolution than women ≥65 years (95% confidence interval, 1.56 -7.02). Women <65 years had a greater reduction in Overactive Bladder Questionnaire Short Form symptom bother scores compared with women ≥65 years by 7.49 points (95% confidence interval, -3.23 to -11.74), regardless of treatment group. There was no difference between quality of life improvement by age. Women ≥65 years had more urinary tract infections following onabotulinumtoxinA and sacral neuromodulation (odds ratio, 1.9, 95% confidence interval, 1.2-3.3). There was no evidence of age differences in sacral neuromodulation revision/removal or catheterization following onabotulinumtoxinA treatment.ConclusionYounger women experienced greater absolute continence, symptom improvement, and fewer urinary tract infections; both older and younger women had beneficial urgency urinary incontinence episode reduction, similar rates of other treatment adverse events, and improved quality of life.

Project description:PURPOSE:We measured urinary biomarker levels in women with refractory urgency urinary incontinence and controls at baseline and 6 months after treatment with sacral neuromodulation or intradetrusor injection of onabotulinumtoxinA. We also assessed the association of baseline biomarkers with posttreatment urgency urinary incontinence episodes and overactive bladder symptom bother outcomes. MATERIALS AND METHODS:First morning urine samples were collected from consented trial participants and age matched women without urgency urinary incontinence. Biomarkers reflecting general inflammation, neuroinflammation, afferent neurotransmitters and tissue remodeling were measured using standardized enzyme-linked immunosorbent assay and activity assays as appropriate. Symptom bother was assessed by the overactive bladder questionnaire and urgency urinary incontinence episodes were determined by bladder diary. Linear models were used to examine differences in mean biomarker levels and the change in urgency urinary incontinence episodes and symptom bother between baseline and 6 months. Modest evidence of a potential association was represented by p ?0.01 and p ?0.004 represented moderate evidence of an association with outcomes. RESULTS:Baseline biomarker levels differed little between cases and controls except tropoelastin (p = 0.001) and N-terminal telopeptide collagen type 1 (p <0.001). Changes in biomarker levels 6 months after intervention included decreases in collagenase (p <0.001) in both treatment groups and increases in interleukin-8 (p = 0.002) and matrix metalloprotease-9 (p <0.001) in the onabotulinumtoxinA group. Higher baseline calcitonin gene-related peptide across both treatments (p = 0.007) and nerve growth factor in the onabotulinumtoxinA arm (p = 0.007) were associated with less reduction in overactive bladder symptom bother. CONCLUSIONS:Refractory urgency urinary incontinence is a complex condition. These data suggest that matrix remodeling and neuropeptide mediation may be involved in its pathophysiological mechanisms and response to treatment.

Project description:ImportanceWomen with refractory urgency urinary incontinence are treated with sacral neuromodulation and onabotulinumtoxinA with limited comparative information.ObjectiveTo assess whether onabotulinumtoxinA is superior to sacral neuromodulation in controlling refractory episodes of urgency urinary incontinence.Design, setting, and participantsMulticenter open-label randomized trial (February 2012-January 2015) at 9 US medical centers involving 381 women with refractory urgency urinary incontinence.InterventionsCystoscopic intradetrusor injection of 200 U of onabotulinumtoxinA (n = 192) or sacral neuromodulation (n = 189).Main outcomes and measuresPrimary outcome, change from baseline mean number of daily urgency urinary incontinence episodes over 6 months, was measured with monthly 3-day diaries. Secondary outcomes included change from baseline in urinary symptom scores in the Overactive Bladder Questionnaire Short Form (SF); range, 0-100, higher scores indicating worse symptoms; Overactive Bladder Satisfaction questionnaire; range, 0-100; includes 5 subscales, higher scores indicating better satisfaction; and adverse events.ResultsOf the 364 women (mean [SD] age, 63.0 [11.6] years) in the intention-to-treat population, 190 women in the onabotulinumtoxinA group had a greater reduction in 6-month mean number of episodes of urgency incontinence per day than did the 174 in the sacral neuromodulation group (-3.9 vs -3.3 episodes per day; mean difference, 0.63; 95% CI, 0.13 to 1.14; P = .01). Participants treated with onabotulinumtoxinA showed greater improvement in the Overactive Bladder Questionnaire SF for symptom bother (-46.7 vs -38.6; mean difference, 8.1; 95% CI, 3.0 to 13.3; P = .002); treatment satisfaction (67.7 vs 59.8; mean difference, 7.8; 95% CI, 1.6 to 14.1; P = .01) and treatment endorsement (78.1 vs 67.6; mean difference; 10.4, 95% CI, 4.3 to 16.5; P < .001) than treatment with sacral neuromodulation. There were no differences in convenience (67.6 vs 70.2; mean difference, -2.5; 95% CI, -8.1 to 3.0; P = .36), adverse effects (88.4 vs 85.1; mean difference, 3.3; 95% CI, -1.9 to 8.5; P = .22), and treatment preference (92.% vs 89%; risk difference, -3%; 95% CI, -16% to 10%; P = .49). Urinary tract infections were more frequent in the onabotulinumtoxinA group (35% vs 11%; risk difference, -23%; 95% CI, -33% to -13%; P < .001). The need for self-catheterization was 8% and 2% at 1 and 6 months in the onabotulinumtoxinA group. Neuromodulation device revisions and removals occurred in 3%.Conclusions and relevanceAmong women with refractory urgency urinary incontinence, treatment with onabotulinumtoxinA compared with sacral neuromodulation resulted in a small daily improvement in episodes that although statistically significant is of uncertain clinical importance. In addition, it resulted in a higher risk of urinary tract infections and need for transient self-catheterizations.

Dataset Information

The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

Publications

The female urinary microbiome: a comparison of women with and without urgency urinary incontinence.

Similar Datasets

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