Urinary microbiome community types associated with urinary incontinence severity in women

Background Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared to controls. Therefore, we hypothesized that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity. Objectives To test if specific urinary or vaginal microbiome community-types are associated with urinary incontinence severity in a population of women with mixed urinary incontinence. Study Design This planned secondary, cross-sectional analysis evaluated associations between the urinary/vaginal microbiomes and urinary incontinence severity in a subset of ESTEEM trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory (UDI) questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected prior to treatment at baseline to assess the urinary and vaginal microbiomes.16S rRNA V4-V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixture methods, samples were clustered into community-types based on core taxa. Associations between community-types and severity measures (UDI total, UDI subscale scores, and the number of urinary incontinence episodes (total, urgency, and stress) from bladder diary) were evaluated using linear regression models adjusted for age and body mass index. Alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were also analyzed for associations with urinary incontinence episodes and community-type. Results Six urinary microbiome community-types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidomonas, Acidovorax, Escherichia, and others). Analysis of urinary incontinence severity in 126 participants with MUI identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (76% mean relative abundance). A community characterized by fewer Lactobacilli (19% mean relative abundance) and greater alpha diversity, was associated with higher total urinary incontinence episodes (2.67 daily leaks, 95% CI: 0.76 - 4.59, p=0.007) and urgency urinary incontinence episodes (1.75 daily leaks, 95% CI: 0.24 - 3.27, p=0.02) compared to the reference group. No significant association was observed between community-type and stress urinary incontinence episodes or UDI total or subscores. The composition of vaginal community-types and urinary community-types were similar but comprised of slightly different bacterial taxa. Vaginal community-types were not associated with urinary incontinence severity, as measured by bladder diary or UDI total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera p=0.01) in urine. Measures of evenness (Shannon/Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes. Conclusions In the urobiome of women with mixed urinary incontinence, a community-type with fewer Lactobacilli and more diverse bacteria was associated with more severe urinary incontinence episodes (total and urgency) compared to a community-type with high predominance of a single genus, Lactobacillus. Whether mixed urinary incontinence severity is due to lesser predominance of Lactobacillus, greater presence of other non-Lactobacillus genera, or the complement of bacteria comprising urobiome community-types, remains to be determined.