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Urinary microbiome community types associated with urinary incontinence severity in women - 06/03/24

Doi : 10.1016/j.ajog.2023.10.036 
Megan U. Carnes, PhD a, , Nazema Y. Siddiqui, MD, MHSc b, Lisa Karstens, PhD c, Marie G. Gantz, PhD a, Darrell L. Dinwiddie, PhD d, Vivian W. Sung, MD, MPH e, Megan Bradley, MD f, Linda Brubaker, MD g, Cecile A. Ferrando, MD, MPH h, Donna Mazloomdoost, MD i, Holly E. Richter, PhD, MD j, Rebecca G. Rogers, MD k, Ariana L. Smith, MD l, Yuko M. Komesu, MD m
On behalf of the

Eunice Kennedy Shriver National Institute of Child Health and Human Development Pelvic Floor Disorders Network

a Social, Statistical, and Environmental Sciences, RTI International, Research Triangle Park, NC 
b Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, Duke University, Durham, NC 
c Division of Bioinformatics and Computational Biomedicine; Division of Urogynecology, Oregon Health & Science University, Portland, OR 
d Division of Genetics, Department of Pediatrics, University of New Mexico Health Sciences Center, Albuquerque, NM 
e Division of Urogynecology, Department of Obstetrics and Gynecology, Warren Alpert Medical School of Brown University, Providence, RI 
f Division of Urogynecology, Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, PA 
g Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California San Diego, San Diego, CA 
h Center for Urogynecology and Pelvic Reconstructive Surgery, Women’s Health Institute, Cleveland Clinic, Cleveland, OH 
i Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD 
j Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, AL 
k Division of Urology, Department of Obstetrics and Gynecology, Albany Medical Center, Albany, NY 
l Division of Urology, Department of Surgery, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 
m Division of Urogynecology, Department of Obstetrics and Gynecology, University of New Mexico Health Sciences and Services Building, Albuquerque, NM 

Corresponding author: Megan U. Carnes, PhD.

Abstract

Background

Urinary microbiome (urobiome) studies have previously reported on specific taxa and community differences in women with mixed urinary incontinence compared with controls. Therefore, a hypothesis was made that higher urinary and vaginal microbiome diversity would be associated with increased urinary incontinence severity.

Objective

This study aimed to test whether 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 and vaginal microbiomes and urinary incontinence severity in a subset of Effects of Surgical Treatment Enhanced With Exercise for Mixed Urinary Incontinence trial participants with urinary incontinence. Incontinence severity was measured using bladder diaries and Urinary Distress Inventory questionnaires collected at baseline. Catheterized urine samples and vaginal swabs were concurrently collected before treatment at baseline to assess the urinary and vaginal microbiomes. Of note, 16S rRNA V4 to V6 variable regions were sequenced, characterizing bacterial taxa to the genus level using the DADA2 pipeline and SILVA database. Using Dirichlet multinomial mixtures methods, samples were clustered into community types based on core taxa. Associations between community types and severity measures (Urinary Distress Inventory total scores, Urinary Distress Inventory subscale scores, and the number of urinary incontinence episodes [total, urgency, and stress] from the bladder diary) were evaluated using linear regression models adjusted for age and body mass index. In addition, alpha diversity measures for richness (total taxa numbers) and evenness (proportional distribution of taxa abundance) were analyzed for associations with urinary incontinence episodes and community type.

Results

Overall, 6 urinary microbiome community types were identified, characterized by varying levels of common genera (Lactobacillus, Gardnerella, Prevotella, Tepidimonas, Acidovorax, Escherichia, and others). The analysis of urinary incontinence severity in 126 participants with mixed urinary incontinence identified a Lactobacillus-dominated reference group with the highest abundance of Lactobacillus (mean relative abundance of 76%). A community characterized by fewer Lactobacilli (mean relative abundance of 19%) and greater alpha diversity was associated with higher total urinary incontinence episodes (2.67 daily leaks; 95% confidence interval, 0.76–4.59; P=.007) and urgency urinary incontinence episodes (1.75 daily leaks; 95% confidence interval, 0.24–3.27; P=.02) than the reference group. No significant association was observed between community type and stress urinary incontinence episodes or Urogenital Distress Inventory total or subscores. The composition of vaginal community types and urinary community types were similar but composed of slightly different bacterial taxa. Vaginal community types were not associated with urinary incontinence severity, as measured by bladder diary or Urogenital Distress Inventory total and subscale scores. Alpha diversity indicated that greater sample richness was associated with more incontinence episodes (observed genera P=.01) in urine. Measures of evenness (Shannon and Pielou) were not associated with incontinence severity in the urinary or vaginal microbiomes.

Conclusion

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 with 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 consisting of urobiome community types remains to be determined.

Le texte complet de cet article est disponible en PDF.

Key words : bladder microbiome, mixed urinary incontinence, urinary incontinence severity, urinary incontinence, urobiome, vaginal microbiome


Plan


 This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institutes of Health Office of Research on Women’s Health (grant numbers: HD041261, HD069013, HD054214, HD054215, HD041267, HD069025, HD069010, HD069006, and HD069031).
 N.Y.S. received authorship royalties from UpToDate, travel stipends from the American Urogynecologic Society (Director At Large), research funding from Medtronic, and research funding from Ethicon Inc. V.W.S. receives editorial stipend from Obstetrics & Gynecology. M.B. receives research funding from Hologic and Axonics Modulation Technologies. L.B. receives editorial stipends from the Journal of the American Medical Association, Urogynecology, and UptoDate. C.A.F. receives authorship royalties from UpToDate, Elsevier, Coloplast, Food and Beverage, and Medtronic. H.E.R. receives research funding from the National Investigation Agency, the University of Texas Southwestern Medical Center, the National Institute of Diabetes and Digestive and Kidney Diseases, the University of North Carolina, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Renovia, REIA, LLC., and Allergan; receives royalties from UpToDate, Obstetrics & Gynecology, and International Urogynecology Journal; receives travel reimbursement related to editor duties; receives funding from the Worldwide Fistula Fund; Data and Safety Monitoring Board BlueWind Medical; Symposia Medicus; and the Center for Human Genetics; receives a speaker fee from the Annual Conference on Obstetrics, Gynecology, Perinatal Medicine, Neonatology, Multi-specialties, and the Law; and receives a consultant fee from Laborie, Palette, Coloplast, and Neomedic. R.G.R receives royalties from UpToDate, receives travel reimbursement and stipend from the International Urogynecological Association for services as editor in chief, and receives travel reimbursement and stipend from the American Board of Obstetrics and Gynecology. A.L.S. receives funding from Food and Beverage and Medtronics. The other authors report no conflict of interest.
 Cite this article as: Carnes MU, Siddiqui NY, Karstens L, et al. Urinary microbiome community types associated with urinary incontinence severity in women. Am J Obstet Gynecol 2024;230:344.e1-20.


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Vol 230 - N° 3

P. 344.e1-344.e20 - mars 2024 Retour au numéro
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