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Incontinence medication response relates to the female urinary microbiota

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Abstract

Introduction and hypothesis

Many adult women have resident urinary bacteria (urinary microbiome/microbiota). In adult women affected by urinary urgency incontinence (UUI), the etiologic and/or therapeutic role of the urinary microbiome/microbiota remains unknown. We hypothesized that microbiome/microbiota characteristics would relate to clinically relevant treatment response to UUI medication per os.

Methods

Adult women initiating medication treatment orally for UUI and a comparator group of unaffected women were recruited in a tertiary care health-care system. All participants provided baseline clinical data and urine samples. Women with UUI were given 5 mg solifenacin, with potential dose escalation to 10 mg for inadequate UUI symptom control at 4 weeks. Additional data and urine samples were collected from women with UUI at 4 and 12 weeks. The samples were assessed using 16S ribosomal RNA (rRNA) gene sequencing and enhanced quantitative urine culturing. The primary outcome was treatment response as measured by the validated Patient Global Symptom Control (PGSC) questionnaire. Clinically relevant UUI symptom control was defined as a 4 or 5 score on the PGSC.

Results

Diversity and composition of the urinary microbiome/microbiota of women with and without UUI differed at baseline. Women with UUI had more bacteria and a more diverse microbiome/microbiota. The clinical response to solifenacin in UUI participants was related to baseline microbiome/microbiota, with responders more likely to have fewer bacteria and a less diverse community at baseline. Nonresponders had a more diverse community that often included bacteria not typically found in responders.

Conclusions

Knowledge of an individual’s urinary microbiome/microbiota may help refine UUI treatment. Complementary tools, DNA sequencing, and expanded urine culture provide information about bacteria that appear to be related to UUI incontinence status and treatment response in this population of adult women.

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Acknowledgments

We kindly thank Mary Tulke RN and Bozena Zemaitaitis for their assistance with participant recruitment and sample collection and Kathleen McKinley MT (ASCP) for her clinical microbiology contributions. We acknowledge and thank the Loyola University Chicago Health Sciences Division’s Office of Informatics and Systems Development for their expertise and for computational resources used in support of this research.

Funding/Support

This study was supported by a grant from the Falk Foundation (LU#202567), by NIH grant R21DK097435-01A1, and by Astellas Scientific and Medical Affairs (ASMA) (Wolfe PI) and is registered at www.clinicaltrials.gov as NCT01642277. Loyola University Chicago Stritch School of Medicine’s research computing facility was developed through grant funds awarded by the Department of Health and Human Services as award number 1G20RR030939-01. The following reagent was obtained through BEI Resources, NIAID, NIH as part of the Human Microbiome Project: Genomic DNA from Microbial Mock Community A (Even, Low Concentration), HM-782D. Our funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript. ASMA was given a courtesy review.

Conflicts of interest

All Authors have completed and submitted ICMJE Form for Disclosure of Potential Conflicts of Interest.

All authors report that this study was funded in part by a grant from Astellas Scientific and Medical Affairs (ASMA).

Alan J. WOLFE, Ph.D. – Scientific Study/Trial: Investigator Initiated Grant from ASMA for certain aspects of this study.

Linda BRUBAKER, MD – Scientific Study/Trial: Grants from NICHD and NIDDK during conduct of a different study. Health Publishing: Personal fees from Up-To-Date.

Elizabeth R. MUELLER, M.D. reports grants from ASMA, during the conduct of the study; grants and personal fees from ASMA, personal fees from Peri-Coach, and personal fees from Allergan, outside the submitted work.

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Author notes

    Authors and Affiliations

    1. Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Krystal J. Thomas-White, Evann E. Hilt, Meghan M. Pearce, Travis K. Price & Alan J. Wolfe

    2. Department of Urology, University of Minnesota, Minneapolis, MN, USA

      Cynthia Fok

    3. Departments of Obstetrics & Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Elizabeth R. Mueller, Cynthia Brincat & Linda Brubaker

    4. Departments of Medicine and Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Stephanie Kliethermes

    5. Department of Obstetrics & Gynecology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Kristin Jacobs

    6. Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Michael J. Zilliox

    7. Center for Biomedical Informatics, Loyola Genomics Facility, Loyola University Chicago, Maywood, IL, USA

      Gina Kuffel

    8. Department of Pathology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Paul Schreckenberger

    9. Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA

      Xiaowu Gai

    10. Departments of Obstetrics and Gynecology and Urology, Division of Female Pelvic Medicine and Reconstructive Surgery, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA

      Elizabeth R. Mueller, Cynthia Brincat & Linda Brubaker

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    Correspondence to Linda Brubaker or Alan J. Wolfe.

    Additional information

    Krystal J. Thomas-White and Evann E. Hilt contributed equally to this work.

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    Thomas-White, K.J., Hilt, E.E., Fok, C. et al. Incontinence medication response relates to the female urinary microbiota. Int Urogynecol J 27, 723–733 (2016). https://doi.org/10.1007/s00192-015-2847-x

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