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女性混合性尿失禁行中段尿道吊带术治疗与泌尿生殖微生物组的相关性研究。

Association between the urogenital microbiome and surgical treatment response in women undergoing midurethral sling operation for mixed urinary incontinence.

机构信息

Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, AL.

Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC.

出版信息

Am J Obstet Gynecol. 2022 Jan;226(1):93.e1-93.e15. doi: 10.1016/j.ajog.2021.07.008. Epub 2021 Jul 21.

Abstract

BACKGROUND

The urogenital microbiome is associated with urgency and mixed urinary incontinence symptoms and differential treatment responses to pharmacotherapy for urgency urinary incontinence.

OBJECTIVE

This 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 DESIGN

This 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.

RESULTS

Objective 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).

CONCLUSION

Women 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.

摘要

背景

泌尿生殖微生物组与紧迫性和混合性尿失禁症状有关,并且对紧迫性尿失禁的药物治疗有不同的治疗反应。

目的

本研究旨在描述女性混合性尿失禁患者行尿道中段吊带术后 12 个月时,术前尿和阴道微生物组是否与手术治疗反应相关。

研究设计

这项队列研究比较了混合性尿失禁试验(NCT01959347)中接受尿道中段吊带术的女性亚组的术前尿液和阴道样本的微生物组组成,并比较了手术应答者和手术无应答者的微生物组。12 个月的客观反应定义为 3 天日记中尿失禁发作次数较基线减少≥70%。主观反应定义为尿生殖窘迫量表评分的基线变化。使用 16S 核糖体 RNA 测序评估细菌丰度和β多样性。使用未调整和年龄调整的线性模型,对与应答者和无应答者相关的主要细菌操作分类单元进行了主要差异丰度分析。

结果

与应答者(n=72)相比,客观无应答者(n=28)年龄更大(58.5±10.7 岁 vs 51.6±10.2 岁),更有可能绝经后未使用激素(比值比,6.4;95%置信区间,1.8-22.6)。应答者和无应答者的阴道和尿微生物组β多样性均与年龄相关(P<.05)。总体而言,主要操作分类单元(属)为乳杆菌属、加德纳菌属、Tepidimonas 属、埃希氏菌属、链球菌属和普雷沃氏菌属。基线尿样中的操作分类单元与手术治疗反应无显著相关性(P 值>.05)。基线阴道乳酸杆菌丰度增加与客观反应相关(P=.04),而普雷沃氏菌与客观无反应相关(P=.01)。调整年龄后,仅基线阴道普雷沃氏菌丰度与客观无反应相关(P=.01)。此外,阴道操作分类单元丰度较低与客观和主观反应以及持续性尿失禁症状相关(P<.05)。

结论

在手术时达到尿失禁治疗发作减少 70%(客观应答者)的女性阴道乳酸杆菌更多;然而,控制年龄会削弱这种关联。在尿道中段吊带术后 1 年尿失禁发作减少未达到 70%的女性,在手术时阴道普雷沃氏菌更多。需要进一步研究以确定改变阴道微生物组的治疗是否会影响混合性尿失禁女性的手术治疗反应。

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