Thomas-White Krystal J, Hilt Evann E, Fok Cynthia, Pearce Meghan M, Mueller Elizabeth R, Kliethermes Stephanie, Jacobs Kristin, Zilliox Michael J, Brincat Cynthia, Price Travis K, Kuffel Gina, Schreckenberger Paul, Gai Xiaowu, Brubaker Linda, Wolfe Alan J
Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
Department of Urology, University of Minnesota, Minneapolis, MN, USA.
Int Urogynecol J. 2016 May;27(5):723-33. doi: 10.1007/s00192-015-2847-x. Epub 2015 Sep 30.
Many adult women have resident urinary bacteria (urinary microbiome/microbiota). In adult women affected by urinary urgency incontinence (UUI), the etiologic and/or therapeutic role of the urinary microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota characteristics would relate to clinically relevant treatment response to UUI medication per os.
Adult women initiating medication treatment orally for UUI and a comparator group of unaffected women were recruited in a tertiary care health-care system. All participants provided baseline clinical data and urine samples. Women with UUI were given 5 mg solifenacin, with potential dose escalation to 10 mg for inadequate UUI symptom control at 4 weeks. Additional data and urine samples were collected from women with UUI at 4 and 12 weeks. The samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced quantitative urine culturing. The primary outcome was treatment response as measured by the validated Patient Global Symptom Control (PGSC) questionnaire. Clinically relevant UUI symptom control was defined as a 4 or 5 score on the PGSC.
Diversity and composition of the urinary microbiome/microbiota of women with and without UUI differed at baseline. Women with UUI had more bacteria and a more diverse microbiome/microbiota. The clinical response to solifenacin in UUI participants was related to baseline microbiome/microbiota, with responders more likely to have fewer bacteria and a less diverse community at baseline. Nonresponders had a more diverse community that often included bacteria not typically found in responders.
Knowledge of an individual's urinary microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA sequencing, and expanded urine culture provide information about bacteria that appear to be related to UUI incontinence status and treatment response in this population of adult women.
许多成年女性存在常驻尿道细菌(尿道微生物群)。在患有尿急失禁(UUI)的成年女性中,尿道微生物群的病因学和/或治疗作用仍不明确。我们假设微生物群特征与口服UUI药物的临床相关治疗反应有关。
在三级医疗保健系统中招募开始口服药物治疗UUI的成年女性以及未受影响女性的对照组。所有参与者提供基线临床数据和尿液样本。患有UUI的女性服用5毫克索利那新,若4周时UUI症状控制不佳,剂量可增至10毫克。在4周和12周时从患有UUI的女性中收集额外数据和尿液样本。使用16S核糖体RNA(rRNA)基因测序和强化定量尿液培养对样本进行评估。主要结局是通过经过验证的患者总体症状控制(PGSC)问卷测量的治疗反应。临床相关的UUI症状控制定义为PGSC评分为4或5分。
有和没有UUI的女性尿道微生物群的多样性和组成在基线时存在差异。患有UUI的女性细菌更多,微生物群更具多样性。UUI参与者对索利那新的临床反应与基线微生物群有关,反应者在基线时细菌数量更可能较少,群落多样性较低。无反应者的群落多样性更高,通常包括反应者中不常见的细菌。
了解个体的尿道微生物群可能有助于优化UUI治疗。DNA测序和扩展尿液培养等辅助工具提供了有关似乎与该成年女性群体中UUI失禁状态和治疗反应相关的细菌的信息。