Symptom improvement with mirabegron treatment is associated with urobiome changes in adult women

Thomas Halverson, Elizabeth R Mueller, Linda Brubaker, Alan J Wolfe, Thomas Halverson, Elizabeth R Mueller, Linda Brubaker, Alan J Wolfe

Abstract

Introduction and hypothesis: Mirabegron, a beta-3 agonist, is prescribed for urgency urinary incontinence (UUI). We assessed the correlation of symptom improvement with urobiome characteristics in adult women participants prescribed mirabegron for UUI treatment.

Methods: We enrolled participants seeking UUI treatment who selected mirabegron and agreed to participate in this 12-week, open label study conducted at the Female Pelvic Medicine and Reconstructive Surgery Center at Loyola University Medical Center. Following eligibility screening and research consent, participants completed the overactive bladder questionnaire (OAB-Q) and provided a catheterized urine sample at baseline, 4, 8, and 12 weeks. The primary outcome, symptom improvement at 12 weeks, was based on the validated Patient Global Symptom Control questionnaire score to dichotomize symptom response (responder vs nonresponder [PGSC score ≤3]). Urine samples were processed by the Expanded Quantitative Urine Culture (EQUC) protocol.

Results: Eighty-three participants (mean age 68 years) completed baseline assessment. Of the 47 participants with primary outcome data and samples analysis, there were 16 responders and 31 nonresponders; responder groups were similar demographically. Living microbes were detected in most participants. There were no significant differences in alpha diversity (within sample) at baseline between groups. However, at the 12-week follow-up, the responder urobiome became significantly richer, with a larger number of genera (p = 0.027) and was significantly more diverse than the nonresponders.

Conclusions: Longitudinal urobiome changes are associated with symptom improvement in adult women being treated with mirabegron for UUI. The mechanism for symptoms improvement may relate to the detected changes in the urobiome and warrants further study.

Trial registration: ClinicalTrials.gov NCT02495389.

Keywords: Expanded quantitative urine culture; Microbiome; Mirabegron; Overactive bladder; Urgency urinary incontinence; Urobiome.

Conflict of interest statement

Dr. Wolfe discloses research support from NIH, the DOD, Astellas Scientific and Medical Affairs and Kimberly Clark Corporation. He also discloses membership of the Scientific Advisory Boards of Pathnostics and Urobiome Therapeutics. Dr. Brubaker discloses research funding from NIH and editorial stipends from Female Pelvic Medicine and Reconstructive Surgery, UpToDate, and JAMA. Dr. Mueller discloses honoraria from UpToDate, Ethicon/Butler-Snow legal defense, and research funding from the National Institutes of Health. The remaining author (T. Halverson) reports no disclosures.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials flow diagram
Fig. 2
Fig. 2
Composite microbiota profiles of responders and nonresponders. Relative abundance of the genera detected in responders and nonresponders at baseline and at 12 weeks

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