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The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls

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Abstract

Introduction & hypothesis

Previous studies have suggested that women with urinary incontinence have an altered urinary microbiome. We hypothesized that the microbiome in women with mixed urinary incontinence (MUI) differed from controls and tested this hypothesis using bacterial gene sequencing techniques.

Methods

This multicenter study compared the urinary microbiome in women with MUI and similarly aged controls. Catheterized urine samples were obtained; v4–6 regions of the 16S rRNA gene were sequenced to identify bacteria. Bacterial predominance (> 50% of an individual’s genera) was compared between MUI and controls. Bacterial sequences were categorized into “community types” using Dirichlet multinomial mixture (DMM) methods. Generalized linear mixed models predicted MUI/control status based on clinical characteristics and community type. Post-hoc analyses were performed in women < 51 and ≥ 51 years. Sample size estimates required 200 samples to detect a 20% difference in Lactobacillus predominance with P < 0.05.

Results

Of 212 samples, 97.6% were analyzed (123 MUI/84 controls, mean age 53 ± 11 years). Overall Lactobacillus predominance did not differ between MUI and controls (45/123 = 36.6% vs. 36/84 = 42.9%, P = 0.36). DMM analyses revealed six community types; communities differed by age (P = 0.001). A High-Lactobacillus (89.2% Lactobacillus) community had a greater proportion of controls (19/84 = 22.6%, MUI 11/123 = 8.9%). Overall, bacterial community types did not differ in MUI and controls. However, post-hoc analysis of women < 51 years found that bacterial community types distinguished MUI from controls (P = 0.041); Moderate-Lactobacillus (aOR 7.78, CI 1.85–32.62) and Mixed (aOR 7.10, CI 1.32–38.10) community types were associated with MUI. Community types did not differentiate MUI and controls in women ≥ 51 years (P = 0.94).

Conclusions

Women with MUI and controls did not differ in overall Lactobacillus predominance. In younger women, urinary bacterial community types differentiated MUI from controls.

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Acknowledgements

The authors thank the research coordinators and all those who made this work possible, including University of Alabama at Birmingham: R. Edward Varner, MD, Robert L. Holley, MD, David R. Ellington, MD, Isuzu Meyer, MD, Alison Parden, MD, Alicia Ballard, MD, Velria Willis, BSN, Nancy Saxon, BSN, and Kathy Carter, BSN. Brown University: Deborah Myers, MD, Charles Rardin, MD, Brittany Star Hampton, MD, Cassandra Carberry, MD, Kyle Wohlrab, MD, Ann Meers, BSN, and Katheryn Rhodes, BA. Cleveland Clinic Foundation: Matthew Barber, MD, Marie Paraiso, MD, Eric Jelovsek, MD, Cecile Unger, MD, Audra Hill, MD, Ly Pung, RN, Kathleen Dastoli, RN, Annette Graham, RN, and Maryori Edington. Duke University: Cindy Amundsen, MD, Anthony Visco, MD, Alison Weidner, MD, Amie Kawasaki, MD, Shantae McLean, Nicole Longoria and Akira Hayes. University of California San Diego: Marianna Alperin, MD, Michael Albo, MD, Laura Aughinbaugh, RNP, Joann Columbo, Cindy Furey, PT, Sherella Johnson, Charles Nager, MD, and Patsy Riley, RN. Kaiser San Diego: Shawn Menefee, MD, Jasmine Tan-Kim, MD, Keisha Dyer, MD, Gouri Diwadkar, MD, Karl Luber, MD, Lynn Hall, RNP, Gisselle Zazueta-Damian and Linda MacKinnon. Kaiser Bellflower: John N. Nguyen, MD, Sharon Jakus-Walkman, MD, Azadeh Rezvan, MD, Christina Liao, MD, Arty Patel, PT, Mary Simmons, PT, Mercedes Cardona and Nancy Flores. University of New Mexico: Gena Dunivan, MD, Peter Jeppson, MD, Sara Cichowski, MD, Karen Taylor, BA, Cassandra Castaneda, BA, Julia Middendorf, BSN, Susan Tigert, BA/BS, Kurt Schwalm, BS, and Amy Overby, BS, CG/MB/PA(ASCP)CM. University of Pennsylvania: Heidi Harvie, MD, Uduak Andy, MD, Lorraine Flick and Michelle Kinglee. University of Pittsburgh: Pamela Moalli, PhD, MD, Michael Bonidie, Gary Sutkin, MD, Jonathan Shepherd, MD, Christopher Chermansky, MD, Judy Gruss, Karen Mislanovich and Lori Geraci. RTI International: Dennis Wallace, PhD, Carolyn Huitema, MS, Michael Ham, BS, and Joshua Levy, MS.

Funding source and sponsor’s role

The Eunice Kennedy Shriver National Institute of Child Health and Human Development sponsored this Pelvic Floor Disorders Network (PFDN) study (1-U10-HD069025–01, 2-U10-HD041261–11, 2-U10-HD041267–12, 1-U10-HD069013–01, 2-U10-HD054214–06, 2-U10-HD054215–06, 1-U10-HD069010–01, 1-U10-HD069006–01, 1-U01HD069031–01). ClinicalTrials.gov Number NCT01959347.

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Correspondence to Yuko M. Komesu.

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Presentation of information in this manuscript

Oral poster presented at the Pelvic Floor Disorders Week Conference (sponsored by the American Urogynecologic Society), October 5, 2017, Providence, Rhode Island; e-oral poster presented at the International Continence Society annual meeting, Florence, Italy, September 13, 2017.

Other support

National Center for Research Resources and the National Center for Advancing Translational Sciences of the National Institutes of Health (grant no. ULTR001449, the University of New Mexico Clinical and Translational Science Center) (for performance of DNA extraction, 16S sequencing).

Author’s potential conflicts of interest/disclosures

Yuko Komesu, MD: Co-PI Grant 1R01AT007171, National Center Complementary and Integrative Health, NIH and “Funding Source” above. Holly Richter, PhD, MD: UpToDate, Renovia. Benjamin Carper: None.Darrell L. Dinwiddie, PhD: None. Emily S. Lukacz, MD: AMS/Astora, Axonics, Boston Scientific, Uroplasty/Coloplast, UptoDate. Nazema Y. Siddiqui, MD: Medtronic. Vivian W. Sung, MD: None. Halina M. Zyczynski, MD: AUGS Board. Beri Ridgeway, MD: Coloplast, Ethicon. Rebecca G. Rogers, MD: UptoDate, ABOG Board member, Transform Trial, International Urogynecology Journal. Lily A. Arya, MD: None. Donna Mazloomdoost, MD: None. Marie G. Gantz, PhD: None.

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Komesu, Y.M., Richter, H.E., Carper, B. et al. The urinary microbiome in women with mixed urinary incontinence compared to similarly aged controls. Int Urogynecol J 29, 1785–1795 (2018). https://doi.org/10.1007/s00192-018-3683-6

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