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

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          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.

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          Most cited references24

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          ICIQ: a brief and robust measure for evaluating the symptoms and impact of urinary incontinence.

          To develop and evaluate the International Consultation on Incontinence Questionnaire (ICIQ), a new questionnaire to assess urinary incontinence and its impact on quality of life (QoL). A developmental version of the questionnaire was produced following systematic literature review and views of an expert committee and patients. Several studies were undertaken to evaluate the psychometric properties of the questionnaire, including content, construct and convergent validity, reliability and sensitivity to change. The ICIQ was easily completed, with low levels of missing data (mean 1.6%). It was able to discriminate among different groups of individuals, indicating good construct validity. Convergent validity was acceptable, with most items demonstrating 'moderate' to 'strong' agreement with other questionnaires. Reliability was good, with 'moderate' to 'very good' stability in test-retest analysis and a Cronbach's alpha of 0.95. Items identified statistically significant reductions in symptoms from baseline following surgical and conservative treatment. Item reduction techniques were used to determine the final version and scoring scheme, which also demonstrated good psychometric properties. The final ICIQ comprises three scored items and an unscored self-diagnostic item. It allows the assessment of the prevalence, frequency, and perceived cause of urinary incontinence, and its impact on everyday life. The ICIQ is a brief and robust questionnaire that will be of use in outcomes and epidemiological research as well as routine clinical practice. Copyright 2004 Wiley-Liss, Inc.
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            Short forms of two condition-specific quality-of-life questionnaires for women with pelvic floor disorders (PFDI-20 and PFIQ-7).

            To develop short forms of 2 valid and reliable condition-specific quality-of-life questionnaires for women with disorders of the pelvic floor including urinary incontinence, pelvic organ prolapse, and fecal incontinence (Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire). Data from the 100 women who contributed to the development and validation of the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire long forms were used to develop the short-form questionnaires. All subsets regression analysis was used to find the items in each scale that best predicted the scale score on the respective long form. When different items appeared equivalent, a choice was made on item content. After development, the short forms and the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire long forms were administered preoperatively to 45 women with pelvic floor disorders scheduled to undergo surgery to evaluate the correlation between short and long forms in a second independent population. The short forms were readministered 3 to 6 months postoperatively to assess the responsiveness of the instruments. The short-form version of the Pelvic Floor Distress Inventory has a total of 20 questions and 3 scales (Urinary Distress Inventory, Pelvic Organ Prolapse Distress Inventory, and Colorectal-Anal Distress Inventory). Each short-form scale demonstrates significant correlation with their long-form scales (r=.86, r=.92, and r=.93, respectively, P<.0001). For the Pelvic Floor Impact Questionnaire short form, the previously developed short form for the Incontinence Impact Questionnaire-7 was used as a template. The 7 items identified in the previously developed Incontinence Impact Questionnaire-7 short form correlate highly with the Incontinence Impact Questionnaire long form (r=.96, P<.0001) as well as the long forms of the Colorectal-Anal Impact Questionnaire scale (r=.96, P<.0001) and the Pelvic Organ Prolapse Impact Questionnaire (r=.94, P<.0001). All subsets regression analysis did not identify any items or combination of items that correlated substantially better for any of the 3 scales. The scales of the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 maintained their excellent correlation to the Pelvic Floor Distress Inventory and Pelvic Floor Impact Questionnaire long forms in the second independent sample (r=.88 to .94 for scales of Pelvic Floor Distress Inventory-20; r=.95 to .96 for scales of Pelvic Floor Impact Questionnaire-7, P<.0001 for all). The test-retest reliability of each scale was good to excellent (intraclass correlation coefficient 0.70 to 0.93, P<.001 for all scales). The scales and summary scores of the Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 demonstrated moderate to excellent responsiveness 3 to 6 months after surgery. The Pelvic Floor Distress Inventory-20 and Pelvic Floor Impact Questionnaire-7 are valid, reliable, and responsive short forms of 2 condition-specific quality-of-life questionnaires for women with pelvic floor disorders.
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              Association between the vaginal microbiota, menopause status, and signs of vulvovaginal atrophy.

              The vaginal microbiota helps protect the female genital tract from disease. We sought to describe the composition of the vaginal microbiota in premenopausal, perimenopausal, and postmenopausal women and to explore the association between the microbiota and vulvovaginal atrophy (VVA). Eighty-seven women (aged 35-60 y) were classified as premenopausal (n = 30), perimenopausal (n = 29), or postmenopausal (n = 28) according to Stages of Reproductive Aging Workshop guidelines. Midvaginal bacterial community composition was characterized by 16S ribosomal RNA gene analysis. Bacterial communities clustered into six community state types (CSTs), of which four were dominated by Lactobacillus crispatus, Lactobacillus gasseri, Lactobacillus iners, or Lactobacillus jensenii, and two (CST IV-A and CST IV-B) had low relative abundance of Lactobacillus. CST IV-A was characterized by Streptococcus and Prevotella, whereas CST IV-B was characterized by Atopobium. There were significant associations between menopause stage and CST (P = 0.004) and between VVA and CST (P = 0.002). Perimenopausal women were more likely to be classified as CST IV-A or L. gasseri CST, whereas postmenopausal women were often classified as CST IV-A. CSTs dominated by L. crispatus and L. iners were more prevalent in premenopausal women. Nineteen participants had signs of mild or moderate VVA. Compared with women with no VVA, the vaginal microbiota of women with mild or moderate atrophy had 25-fold greater odds of being classified as CST IV-A versus L. crispatus CST (adjusted odds ratio, 25.89; 95% credible interval, 2.98-406.79). A distinct bacterial community state (CST IV-A) with a low relative abundance of Lactobacillus is associated with VVA. Future studies recruiting a larger number of women are needed to replicate the findings. This study provides an impetus for future longitudinal studies designed to manage, modulate, and restore vaginal microbiota homeostasis, which would provide stronger evidence for a causal relationship with VVA and ultimately improve the treatment and prevention of atrophic vaginitis in menopause.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                27 July 2016
                2016
                : 6
                : 78
                Affiliations
                [1] 1Division of Bioinformatics and Computational Biology, Oregon Health and Science University Portland, OR, USA
                [2] 2Division of Urogynecology, Oregon Health and Science University Portland, OR, USA
                [3] 3Division of Arthritis and Rheumatology, Oregon Health and Science University Portland, OR, USA
                [4] 4Department of Behavioral Neuroscience, Oregon Health and Science University Portland, OR, USA
                [5] 5Department of Psychiatry, Oregon Health and Science University Portland, OR, USA
                [6] 6Advanced Imaging Research Center, Oregon Health and Science University Portland, OR, USA
                [7] 7Devers Eye Institute, Oregon Health and Science University Portland, OR, USA
                [8] 8Kaiser Permanente Clackamas, OR, USA
                Author notes

                Edited by: Thomas A. Ficht, Texas A&M University, USA

                Reviewed by: Deborah Threadgill, Texas A&M University, USA; Bassam Abomoelak, Orlando Health, USA

                *Correspondence: Rahel Nardos nardosr@ 123456ohsu.edu
                Article
                10.3389/fcimb.2016.00078
                4961701
                27512653
                f1fe88bc-0a85-4b8a-9f80-add1d69e2e7b
                Copyright © 2016 Karstens, Asquith, Davin, Stauffer, Fair, Gregory, Rosenbaum, McWeeney and Nardos.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 April 2016
                : 12 July 2016
                Page count
                Figures: 6, Tables: 3, Equations: 0, References: 46, Pages: 13, Words: 8310
                Funding
                Funded by: Collins Medical Trust 10.13039/100002028
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: K12 HD 043488
                Award ID: UL1TR000128
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development 10.13039/100009633
                Award ID: BIRCWH K12
                Funded by: Office of Research on Women's Health 10.13039/100000124
                Award ID: K12 HD 043488
                Funded by: National Center for Advancing Translational Sciences 10.13039/100006108
                Award ID: UL1TR000128
                Funded by: Oregon Clinical and Translational Research Institute 10.13039/100007804
                Award ID: UL1TR000128
                Categories
                Microbiology
                Original Research

                Infectious disease & Microbiology
                bladder disease,bladder microbiome,urinary microbiome,overactive bladder,human microbiome,urinary incontinence,urge

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