Microbiome Predictors of Surgical Treatment Response in Women Undergoing Mid-urethral Sling Surgery for Mixed Urinary Incontinence

Richter H1, Carnes M2, Komesu Y3, Lukacz E4, Rogers R5, Siddiqui N6, Arya L7, Sung V8, Bradley M9, Carper B2, Donna M10, Dinwiddie D3, Gantz M2

Research Type

Clinical

Abstract Category

Female Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 600
Infection and Pot Pourri
Scientific Podium Short Oral Session 38
On-Demand
Female Mixed Urinary Incontinence Basic Science
1. University of Alabama at Birmingham, 2. RTI International, 3. University of New Mexico, 4. University of California, San Diego, 5. University of Texas at Austin, 6. Duke University, 7. University of Pennsylvania, 8. Brown University, 9. University of Pittsburgh, 10. Eunice Kennedy Shriver National Institute of Child Health and Human Development
Presenter
H

Holly E Richter

Links

Abstract

Hypothesis / aims of study
Describe pre-operative urinary and vaginal bacterial taxa associated with 12 month surgical response after mid-urethral sling in women with mixed urinary incontinence.
Study design, materials and methods
After Institutional Board Approval and written informed consent was obtained, urine and vaginal bacterial samples (N=124) were collected from a subset of women with MUI enrolled in the ESTEEM trial (NCT01959347). All women underwent midurethral sling surgery. Objective response at 12 months was defined as ≥70% reduction from baseline in urinary incontinence episodes on 3-day diary without additional treatment. Based on mixed urinary incontinence symptoms as measured by the Urogenital Distress Inventory, as most subjects responded to treatment meeting the minimal clinically important difference threshold, subjective response was defined by change from baseline in Urogenital Distress Inventory analyzed continuously. Clinical and demographic differences in responder status were assessed with univariate generalized linear models and Fischer’s exact test. Using 16S rRNA gene sequencing data, beta diversity was compared in responders vs non-responders. Differential abundance analysis of operational taxonomic units was assessed, focusing on predominant taxa defined as the most prevalent operational taxonomic units in ≥3 participants, using unadjusted and age-adjusted linear models.
Results
Objective responders (N=72), compared to non-responders (N=28) were younger (51.6±10.2 y, p = 0.007), premenopausal (OR [CI] 4.22 [1.28-13.86]) and on hormone replacement therapy (HRT), (OR [CI] 6.35 [1.82-22.23]. Age (urine and vagina, p<0.001), menstrual status (urine, p=0.04; vagina, p=0.01), postmenopausal +HRT (vagina, p=0.01) and responder status (vagina, p=0.03) were associated with operational taxonomic units in beta diversity analyses. Six predominant operational taxonomic units were identified: Lactobacillus, most predominant (urine and vagina), followed by Gardnerella (urine and vagina), Tepidomonas (urine), Escherichia (urine), Streptococcus (urine and vagina), Prevotella (urine and vagina). Differential abundance analysis of urine revealed no association between predominant operational taxonomic units and responder status. Vaginal differential abundance analysis adjusting for age, found Prevotella associated with objective responder status, p=0.01; changes in Urogenital Distress Inventory (N=105) scores were not associated with vaginal operational taxonomic units (Fig. 1a, b). Lower Lactobacillus was associated with older age and higher Prevotella (Fig. 2).
Interpretation of results
In older women undergoing a mid-urethral sling for the treatment of mixed urinary incontinence, the state of the vaginal microbiome may be important in optimizing surgical outcomes.
Concluding message
Surgical responders had decreased Prevotella in the vagina. Younger women, more likely to be surgical responders, had more Lactobacillus. Further research is needed to confirm whether therapy altering the vaginal microbiome in older women impacts surgical response in women with mixed urinary incontinence.
Figure 1 Figure 1a-b
Figure 2 Figure 2
Disclosures
Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development Clinical Trial Yes Registration Number NCT01959347 RCT Yes Subjects Human Ethics Committee Institutional Review Board Helsinki Yes Informed Consent Yes