Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, 60153, USA.
Division of Female Pelvic Medicine and Reconstructive Surgery, Departments of Urology & Obstetrics/Gynecology, Loyola University Medical Center, Maywood, IL, USA.
Int Urogynecol J. 2023 Jun;34(6):1271-1277. doi: 10.1007/s00192-022-05416-x. Epub 2022 Nov 24.
Representatives of two classes of oral medication are often used to treat urgency urinary incontinence (UUI): solifenacin, an M3-receptor-selective antimuscarinic, and mirabegron, a beta-3 agonist. Two previous asynchronous drug-specific studies suggested different interactions between these medications and the urobiome despite identical methodologies, including recruitment, sample procurement, medication dose escalation strategy, determination of 12-week responders versus nonresponders, and data collection. This analysis compares data from these two studies using a uniform analytic approach.
Urine was collected aseptically via transurethral catheter from consenting participants for subsequent processing by the Expanded Quantitative Urine Culture (EQUC) protocol in two cohorts (n=50 and n=47) that were demographically similar. Species accumulation curves were generated to compare the total number of unique species detected. Indices that measure richness, evenness, and/or abundance were used to compare alpha (within sample) diversity. The Bray-Curtis Dissimilarity Index was used to determine between sample (beta) diversity.
The majority of the 40 species detected in the pre-treatment urobiomes were detected in both cohorts. Both pre-treatment urobiomes were substantially similar in species richness, evenness, and diversity. Differences in pre-treatment urobiomes were associated with treatment response for solifenacin-treated participants only. In contrast, the pre-treatment urobiomes of mirabegron-treated participants were not associated with treatment response. Changes in the post-treatment urobiomes were detected in both cohorts with an increase in richness for both solifenacin (5-mg dose only) and mirabegron.
Pre-treatment urobiome characteristics were associated with treatment response in participants treated with solifenacin, but not mirabegron. Differences exist in urobiome response after treatment with two medications that have known differences in mechanism of action.
有两类口服药物常被用于治疗急迫性尿失禁（UUI）：索利那新，一种 M3 受体选择性抗毒蕈碱药物；米拉贝隆，一种β3 激动剂。尽管采用了相同的方法，包括招募、样本采集、药物剂量递增策略、确定 12 周的反应者与非反应者以及数据收集，但两项先前的非同步药物特异性研究表明，这两种药物与尿生物群之间存在不同的相互作用。本分析使用统一的分析方法比较了这两项研究的数据。
通过经尿道导尿无菌采集同意参与者的尿液，随后通过 Expanded Quantitative Urine Culture（EQUC）方案进行处理，这两个队列（n=50 和 n=47）在人口统计学上相似。生成物种累积曲线以比较检测到的独特物种总数。使用衡量丰富度、均匀度和/或丰度的指数来比较α（样本内）多样性。Bray-Curtis 不相似性指数用于确定样本间（β）多样性。
在预处理尿生物群中检测到的 40 个物种中的大多数在两个队列中都有检测到。预处理尿生物群在物种丰富度、均匀度和多样性方面非常相似。只有接受索利那新治疗的参与者的预处理尿生物群与治疗反应存在差异。相比之下，接受米拉贝隆治疗的参与者的预处理尿生物群与治疗反应无关。在两个队列中都检测到了治疗后尿生物群的变化，索利那新（仅 5mg 剂量）和米拉贝隆的丰富度都有所增加。
在接受索利那新治疗的参与者中，预处理尿生物群特征与治疗反应相关，但在接受米拉贝隆治疗的参与者中则没有。两种具有不同作用机制的药物治疗后，尿生物群反应存在差异。
