Association Between the Urogenital Microbiome and Surgical Treatment Response in Women Undergoing Mid-urethral Sling Surgery for Mixed Urinary Incontinence.

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

To describe whether the preoperative urinary and vaginal microbiomes were associated with treatment response 12-months after mid-urethral sling surgery in women with mixed urinary incontinence.

This cohort study compared the preoperative microbiome compositions of urine and vaginal samples from a subset of women undergoing mid-urethral sling surgery in the ESTEEM (Effects of Surgical Treatment Enhanced with Exercise for Mixed Urinary Incontinence) trial (NCT01959347) and compared the microbiota in women who were surgical responders versus surgical non-responders. Twelve-month objective response was defined as a ≥70% reduction from baseline urinary incontinence episodes on three-day diary. Subjective response was defined as change from baseline in Urogenital Distress Inventory scores. Bacterial abundance and beta diversity were assessed using 16S rRNA (ribosomal ribonucleic acid) sequencing. The primary differential abundance analysis described predominant bacterial operational taxonomic units associated with responders vs. non-responders using unadjusted and age-adjusted linear models.

Objective non-responders (N=28) compared to responders (N=72) were older (58.5±10.7 vs 51.6±10.2 years) and more likely post-menopausal without hormone use (Odds Ratio [95% Confidence Interval] 6.4 [1.8-22.6]). Vaginal and urinary microbiota beta diversity was associated with age (p<0.05) for both responders and non-responders. Overall predominant operational taxonomic units (genera) were: Lactobacillus, Gardnerella, Tepidomonas, Escherichia, Streptococcus, and Prevotella. Operational taxonomic units from baseline urine samples were not significantly associated with treatment response. A greater abundance of baseline vaginal Lactobacillus was associated with objective response(p=0.04) and Prevotella with objective non-response (p=0.01). Adjusting for age, only a greater abundance of baseline vaginal Prevotella was associated with objective non-response (p=0.01). Less abundant vaginal operational taxonomic units were also associated with objective and subjective responses and persistent urinary incontinence symptoms (p<0.05).

Women meeting a 70% reduction of urinary incontinence treatment episodes (objective responders) had greater vaginal Lactobacillus at the time of surgery, however controlling for age diminished this association. Women not meeting a 70% reduction of urinary incontinence episodes one year after mid-urethral sling surgery had greater vaginal Prevotella at the time of mid-urethral sling surgery. Further research is needed to determine whether therapy altering the vaginal microbiome may impact surgical treatment response in women with mixed urinary incontinence.

American journal of obstetrics and gynecology. 2021 Jul 20 [Epub ahead of print]

Holly E Richter, Megan U Carnes, Yuko M Komesu, Emily S Lukacz, Lily Arya, Megan Bradley, Rebecca G Rogers, Vivian W Sung, Nazema Y Siddiqui, Benjamin Carper, Donna Mazloomdoost, Darryl Dinwiddie, Marie G Gantz, NICHD Pelvic Floor Disorders Network

Obstetrics & Gynecology, University of Alabama at Birmingham, Birmingham, AL, United States. Electronic address: ., Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, United States., Obstetrics & Gynecology, University of New Mexico Health Sciences Center, Albuquerque, NM, United States., Department of Obstetrics, Gynecology & Reproductive Sciences, University of California San Diego, San Diego, CA, United States., Obstetrics & Gynecology, University of Pennsylvania School of Medicine, Philadelphia, PA, United States., Obstetrics & Gynecology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States., Obstetrics & Gynecology, Dell Medical School University of Texas Austin, Austin TX, United States., Obstetrics & Gynecology, Alpert Medical School of Brown University, Providence, RI, United States., Obstetrics & Gynecology, Duke University, Durham, NC, United States., Gynecologic Health and Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) National Institutes of Health (NIH), Bethesda, MD, United States., Pediatrics, Clinical Translational Science Center, University of New Mexico Health Sciences, Albuquerque, NM, United States.