title: Incontinence medication response relates to the female urinary microbiota.
abstract: OBJECTIVE
  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.
authors.affiliation: Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Krystal J
authors.initials: KJ
authors.lastname: Thomas-White
authors.affiliation: Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Evann E
authors.initials: EE
authors.lastname: Hilt
authors.affiliation: Department of Urology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Fok
authors.affiliation: Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Meghan M
authors.initials: MM
authors.lastname: Pearce
authors.affiliation: Departments of Obstetrics & Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.|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.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Mueller
authors.affiliation: Departments of Medicine and Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kliethermes
authors.affiliation: Department of Obstetrics & Gynecology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Jacobs
authors.affiliation: Department of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zilliox
authors.affiliation: Departments of Obstetrics & Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.|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.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Brincat
authors.affiliation: Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Travis K
authors.initials: TK
authors.lastname: Price
authors.affiliation: Center for Biomedical Informatics, Loyola Genomics Facility, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Gina
authors.initials: G
authors.lastname: Kuffel
authors.affiliation: Department of Pathology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Schreckenberger
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Gai
authors.affiliation: Departments of Obstetrics & Gynecology and Urology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. lbrubaker@luc.edu.|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. lbrubaker@luc.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Brubaker
authors.affiliation: Departments of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA. awolfe@luc.edu.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Wolfe
mesh_terms: D000190:Actinomyces / Q000302:isolation & purification; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D001437:Bacteriuria / Q000382:microbiology*; D016022:Case-Control Studies; D015169:Colony Count, Microbial; D003352:Corynebacterium / Q000302:isolation & purification; D005260:Female; D006801:Humans; D007778:Lactobacillus / Q000302:isolation & purification; D064307:Microbiota; D008875:Middle Aged; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D000069464:Solifenacin Succinate / Q000008:administration & dosage / Q000627:therapeutic use*; D013291:Streptococcus / Q000302:isolation & purification; D016896:Treatment Outcome; D053202:Urinary Incontinence, Urge / Q000188:drug therapy* / Q000382:microbiology*; D014551:Urinary Tract / Q000382:microbiology*
chemical_list: D018727:Muscarinic Antagonists; D012336:RNA, Ribosomal, 16S; D000069464:Solifenacin Succinate
keywords: Clinical microbiology; Solifenacin; Urinary incontinence