The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls.
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ABSTRACT:
SUBMITTER: Komesu YM
PROVIDER: S-EPMC6295358 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
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The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls.
Komesu Yuko M YM Richter Holly E HE Carper Benjamin B Dinwiddie Darrell L DL Lukacz Emily S ES Siddiqui Nazema Y NY Sung Vivian W VW Zyczynski Halina M HM Ridgeway Beri B Rogers Rebecca G RG Arya Lily A LA Mazloomdoost Donna D Gantz Marie G MG
International urogynecology journal 20180616 12
<h4>Introduction & hypothesis</h4>Previous studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques.<h4>Methods</h4>This multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4-6 regions of the 16S r ...[more]
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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.
| S-EPMC5433900 | biostudies-literature
Project description: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.
| S-EPMC4161260 | biostudies-literature
Project description:BackgroundThe urogenital microbiome is associated with urgency and mixed urinary incontinence symptoms and differential treatment responses to pharmacotherapy for urgency urinary incontinence.ObjectiveThis study aimed to describe whether the preoperative urinary and vaginal microbiomes were associated with surgical treatment responses at 12 months after a midurethral sling operation in women with mixed urinary incontinence.Study designThis cohort study compared the preoperative microbiome compositions of urine and vaginal samples from a subset of women undergoing a midurethral sling operation in the Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial (NCT01959347) and compared the microbiota in women who were surgical responders vs surgical nonresponders. Twelve-month objective response was defined as a ≥70% reduction from baseline urinary incontinence episodes on a 3-day diary. Subjective response was defined as a change from baseline in the Urogenital Distress Inventory scores. Bacterial abundance and beta diversity were assessed using 16S ribosomal RNA sequencing. The primary differential abundance analysis described predominant bacterial operational taxonomic units associated with responders vs nonresponders using unadjusted and age-adjusted linear models.ResultsObjective nonresponders (n=28) compared with responders (n=72) were older (58.5±10.7 vs 51.6±10.2 years) and more likely postmenopausal without hormone use (odds ratio, 6.4; 95% confidence interval, 1.8-22.6). Vaginal and urinary microbiota beta diversities were associated with age (P<.05) for both responders and nonresponders. Overall, predominant operational taxonomic units (genera) were Lactobacillus, Gardnerella, Tepidimonas, Escherichia, Streptococcus, and Prevotella. Operational taxonomic units from baseline urine samples were not significantly associated (P threshold=.05) with surgical treatment responses. A greater abundance of baseline vaginal Lactobacillus was associated with an objective response (P=.04) and Prevotella with an objective nonresponse (P=.01). Adjusting for age, only a greater abundance of baseline vaginal Prevotella was associated with an objective nonresponse (P=.01). Moreover, less abundant vaginal operational taxonomic units were associated with objective and subjective responses and persistent urinary incontinence symptoms (P<.05).ConclusionWomen meeting a 70% reduction of urinary incontinence treatment episodes (objective responders) had greater vaginal Lactobacillus at the time of the surgical procedure; however, controlling for age diminished this association. Women not meeting a 70% reduction of urinary incontinence episodes 1 year after a midurethral sling operation had greater vaginal Prevotella at the time of the midurethral sling operation. Further research is needed to determine whether therapy altering the vaginal microbiome may impact surgical treatment responses in women with mixed urinary incontinence.
| S-EPMC8748268 | biostudies-literature
Project description:ObjectiveThe purpose of this study was to characterize the urinary microbiota in women who are planning treatment for urgency urinary incontinence and to describe clinical associations with urinary symptoms, urinary tract infection, and treatment outcomes.Study designCatheterized urine samples were collected from multisite randomized trial participants who had no clinical evidence of urinary tract infection; 16S ribosomal RNA gene sequencing was used to dichotomize participants as either DNA sequence-positive or sequence-negative. Associations with demographics, urinary symptoms, urinary tract infection risk, and treatment outcomes were determined. In sequence-positive samples, microbiotas were characterized on the basis of their dominant microorganisms.ResultsMore than one-half (51.1%; 93/182) of the participants' urine samples were sequence-positive. Sequence-positive participants were younger (55.8 vs 61.3 years old; P = .0007), had a higher body mass index (33.7 vs 30.1 kg/m(2); P = .0009), had a higher mean baseline daily urgency urinary incontinence episodes (5.7 vs 4.2 episodes; P < .0001), responded better to treatment (decrease in urgency urinary incontinence episodes, -4.4 vs -3.3; P = .0013), and were less likely to experience urinary tract infection (9% vs 27%; P = .0011). In sequence-positive samples, 8 major bacterial clusters were identified; 7 clusters were dominated not only by a single genus, most commonly Lactobacillus (45%) or Gardnerella (17%), but also by other taxa (25%). The remaining cluster had no dominant genus (13%).ConclusionDNA sequencing confirmed urinary bacterial DNA in many women with urgency urinary incontinence who had no signs of infection. Sequence status was associated with baseline urgency urinary incontinence episodes, treatment response, and posttreatment urinary tract infection risk.
| S-EPMC4556587 | biostudies-literature
Project description:The aim of this debate article is to discuss whether effective treatments are available for mixed urinary incontinence (MUI). Because patients with MUI have both stress and urgency urinary incontinence (SUI and UUI) episodes and current treatment guidelines currently recommend treating the predominant symptom first, this article presents standard and emerging treatments for both SUI and UUI before discussing how well these treatments meet the medical needs of patients with MUI. Standard treatments presented include noninvasive options such as lifestyle changes and pelvic floor exercises, pharmacological agents, and surgery. Treatment of all three types of urinary incontinence (UI) is usually initiated with noninvasive options, after which treatment options diverge based on UI subtype. Multiple pharmacological agents have been developed for the treatment of UUI and overactive bladder, whereas surgery remains the standard option for SUI and stress-predominant MUI. The divide between UUI and SUI options seems to be propagated in emerging treatments, with most novel pharmacological agents still targeting UUI and even having SUI and stress-predominant MUI as exclusion criteria for participation in clinical trials. Considering that current treatment options focus almost exclusively on treating the predominant symptom of MUI and that emerging pharmacological treatments exclude patients with stress-predominant MUI during the development phase, effective treatments for MUI are lacking both in standard and emerging practice. Ideally, agents with dual mechanisms of action could provide symptom benefit for both the stress and urgency components of MUI.
| S-EPMC10092712 | biostudies-literature
Project description:To estimate whether perioperative and postoperative outcomes after Burch colposuspension or pubovaginal sling for stress urinary incontinence (SUI) differed with age.This study was a prospective secondary analysis of the Stress Incontinence Surgical Treatment Efficacy Trial. Baseline characteristics, adverse events, and 2-year outcomes of women at least 65 years old were compared with those younger than 65 years using chi(2) and t tests. Multivariable analyses were performed, including age and outcomes that differed between age groups on univariable analysis, adjusting for variables that differed by age group at baseline and by surgical treatment group.Six-hundred fifty-five women were included in analyses of perioperative events and 520 for 2-year outcomes. Mean age (+/-standard deviation) was 69.7 (+/-3.7) years in the older group and 49.4 (+/-8.2) in the younger group. Older women had slightly longer time to normal activities (50 days compared with 42 days, P=.05), but there was no difference in time to normal voiding (14 days compared with 11 days, P=.42). Older women were more likely to have a positive stress test at follow-up (odds ratio [OR] 3.7, 95% confidence interval [CI] 1.70-7.97, P=.001), less subjective improvement in stress (8 point lesser decrease, 95% CI 1.5-14.1, P=.02), and urge incontinence (7 point lesser decrease, 95% CI 1.5-12.2, P=.01) by the Medical and Epidemiologic Social Aspects of Aging questionnaire, and were more likely to undergo surgical retreatment for SUI (OR 3.9, 95% CI 1.30-11.48). Perioperative adverse events and length of stay did not differ between groups.Older women undergoing surgery for stress incontinence can expect to do as well as younger women with respect to perioperative outcomes, but experience 2-year outcomes that are worse.
| S-EPMC2626173 | biostudies-literature
Project description:Introduction and hypothesisThis study's aims were to detect and quantify bacterial DNA in the urine of randomized trial participants about to undergo treatment for urinary urgency incontinence (UUI) without clinical evidence of urinary tract infection (UTI) and to determine if the presence of bacterial DNA in baseline urine relates to either baseline urinary symptoms or UTI risk after urinary tract instrumentation.MethodsWomen without clinical evidence of baseline UTI were randomized to cystoscopic onabotulinum toxin A injection and oral placebo medication versus cystoscopic placebo injection and active oral medication. Bacterial DNA in participants' catheterized urine was measured by quantitative polymerase chain reaction (qPCR).ResultsBacterial DNA was detected in the urine of 38.7 % of participants (60 out of 155). In these 60 qPCR-positive participants, baseline daily UUI episodes were greater than in the 95 qPCR-negative participants (5.71 [±2.60] vs 4.72 [±2.86], p = 0.004). Neither symptom severity by questionnaire nor treatment outcome was associated with qPCR status or with qPCR level in qPCR-positive subjects. In contrast, the presence of urinary bacterial DNA was associated with UTI risk: only 10 % of the qPCR-positive women developed a UTI post-treatment, while 24 % of the qPCR-negative women did so. The median qPCR level for qPCR-positive samples did not differ significantly by UTI status (UTI 2.58 × 10(5) vs no UTI 1.35 × 10(5) copies/mL, p = 0.6).ConclusionsThese results may indicate a urinary bacterial contribution to both baseline UUI and the risk of post-treatment UTI.
| S-EPMC4128900 | biostudies-literature
Project description:AIMS:The primary aim is to provide detailed rationale and methodology for the development and implementation of a perioperative behavioral/pelvic floor exercise research protocol for women who self-chose surgical intervention and who may or may not have been offered behavioral treatments initially. This protocol is part of the ESTEEM trial (Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence Trial) which was designed to determine the effect of a combined surgical and perioperative behavioral/pelvic floor exercise intervention versus surgery alone on improving mixed urinary incontinence (MUI) and overactive bladder (OAB) symptoms. METHODS:As part of a multi-site, prospective, randomized trial of women with MUI electing midurethral sling (MUS) surgical treatment, participants were randomized to a standardized perioperative behavioral/pelvic floor exercise intervention?+?MUS versus MUS alone. The specific behavioral intervention included: education on voiding habits, pelvic floor muscle training (PFMT), bladder training (BT), strategies to control urgency and reduce/prevent urinary symptoms, and monitoring/promoting adherence to behavioral recommendations. To ensure consistency across all eight research sites in the pelvic floor disorders network (PFDN), selective behavioral treatments sessions were audiotaped and audited for protocol adherence. RESULTS:The behavioral intervention protocol includes individualization of interventions using an algorithm based on pelvic floor muscle (PFM) assessment, participant symptoms, and findings from the study visits. We present, here, the specific perioperative behavioral/pelvic floor exercise interventions administered by study interventionists. CONCLUSIONS:This paper details a perioperative behavioral/pelvic floor exercise intervention research study protocol developed for women undergoing surgery for MUI.
| S-EPMC5907803 | biostudies-literature
Project description:ObjectiveTo develop an empirically derived definition of mixed urinary incontinence (MUI) for use in incontinence outcomes research.MethodsParticipants in a randomized trial comparing the fascial sling and. Burch colposuspension were assessed using standardized measures including the Medical, Epidemiologic and Social Aspects of Aging (MESA), UI questionnaire, the Urogenital Distress Inventory (UDI), 3-day urinary diary and urodynamic studies (UDS). Participants were required to have stress incontinence with a MESA stress subscale score > MESA urge subscale score. Several definitions of MUI were considered. Logistic and linear regression analysis methods were used to predict clinical outcomes based on the different MUI definitions. Analyses were carried out using SAS (SAS Institute, Inc., Cary, NC, Version 9.1). Statistical significance was defined at P-value <0.05.ResultsIn 655 participants, the proportion of women with MUI varied from 8.3% to 93.3% depending on the MUI definition All definitions were associated with severity as measured by the frequency of incontinence episodes at baseline; however little of the variability was explained by any single definition. No strict cut-off value for these baseline measures was identified to predict clinical outcomes.ConclusionsThese MUI definitions do not adequately categorize clinically relevant UI subgroups. For research reporting, MUI subcomponents of stress and urge UI should be described separately rather than as a single dimension.
| S-EPMC2702259 | biostudies-literature
Project description:Urinary incontinence in women is a common problem. With increasing age its prevalence and severity of its manifestations increase. Among nursing home residents the frequency is between 43 and 77 %, 6 to 10 % of all admissions to nursing homes are due to urinary incontinence. The risk for urinary incontinence among women with cognitive deficits is 1.5- to 3.4-fold higher than for women without mental disorders. The most common form is stress incontinence (50 %), followed by mixed stress-urge incontinence (40 %) and purely urge incontinence (OAB = overactive bladder, 20 %). With regard to its cause, the latter remains unclarified in about 80 % of the cases. It is often difficult to treat. There are also cases in which urge incontinence is related to traumatic events. In such cases behavioural and psychotherapeutic options may be helpful. Almost inevitably every form of incontinence has psychological consequences: shame and insecurity are often results of uncontrolled loss of urine. Among others, in the long term, they lead to the avoidance of social contacts and possibly to depression and isolation. Consideration of the psychosomatics is important in the therapy for female urinary incontinence from three points of view: 1) the efficacy of treatment is better suited to the patient, 2) the treatment costs are lower, 3) the professional satisfaction of the responsible physician increases.
| S-EPMC4361165 | biostudies-literature