Pd12-06 the Impact of Urinary Microbiota Composition on Immune and Inflammatory Responses in a Healthy Mouse Model

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology (PD12)1 May 2024PD12-06 THE IMPACT OF URINARY MICROBIOTA COMPOSITION ON IMMUNE AND INFLAMMATORY RESPONSES IN A HEALTHY MOUSE MODEL Dalia Othman, Igor Moskalev, Ana Luque-Badillo, Cesar Monjaras-Avila, Sarah Hanstock, Felipe Eltit, Sheryl Munshan, Breanna Nelson, Alberto Contreras-Sanz, Peter Black, and Dirk Lange Dalia OthmanDalia Othman , Igor MoskalevIgor Moskalev , Ana Luque-BadilloAna Luque-Badillo , Cesar Monjaras-AvilaCesar Monjaras-Avila , Sarah HanstockSarah Hanstock , Felipe EltitFelipe Eltit , Sheryl MunshanSheryl Munshan , Breanna NelsonBreanna Nelson , Alberto Contreras-SanzAlberto Contreras-Sanz , Peter BlackPeter Black , and Dirk LangeDirk Lange View All Author Informationhttps://doi.org/10.1097/01.JU.0001008772.30001.48.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Recent discoveries identified the existence of the urinary microbiota in the bladder. Although previous work has investigated urinary microbiota composition across healthy and diseased states, no efforts have explored its actual role in the bladder. Given pre-existing evidence that commensal microbiota affects immune responses, we hypothesize the urinary microbiota of the bladder may affect the local immune response. In bladder cancer (BCa), intravesical Bacillus Calmette-Guérin (BCG) treatment acts as an immunostimulatory agent to prevent recurrence in non-muscle invasive bladder cancer (NMIBC). The objective of this study was to examine the role of urinary microbiota composition in determining bladder immune responses in a healthy environment, using BCG as an immunostimulatory agent. METHODS: To assess the role of the urinary microbiome on the BCG-induced inflammatory response, mice underwent ultrasound-guided instillation of BCG into the bladder lumen. The mice had either a healthy or a disrupted urinary microbiota. Disruption was achieved through antibiotic (gentamicin or clindamycin) instillation prior to BCG treatment. Whole bladder, spleen, and bladder-draining lymph node tissue was collected to assess changes in immune cell populations through fluorescence-activated cell sorting (FACS) and histology. RESULTS: FACS analysis observed significant shifts across immune cell populations. Gentamicin instillation induced a pro-inflammatory environment through elevated M1 and reduced M2 macrophages, compared to control. Subsequent BCG treatment shifted the environment towards an anti-inflammatory response by increasing M2 and reducing M1 macrophages, which was also observed in mice with a healthy microbiota. Immunohistochemistry of bladder tissue similarly reflected the FACs analysis findings. Hematoxylin and eosin staining of bladder sections demonstrated significant irritation of the urothelium lining, with urothelial cell shedding observed. CONCLUSIONS: Urinary microbiota composition may be an important mediator of immune responses in the healthy bladder. Current work is investigating its impact on mediating key immune responses in the treatment of NMIBC, as it may be a target to improve responsiveness to BCG treatment. Source of Funding: Lotte & John Hecht Memorial FoundationCanadian Urological Association Scholarship Foundation © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e258 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Dalia Othman More articles by this author Igor Moskalev More articles by this author Ana Luque-Badillo More articles by this author Cesar Monjaras-Avila More articles by this author Sarah Hanstock More articles by this author Felipe Eltit More articles by this author Sheryl Munshan More articles by this author Breanna Nelson More articles by this author Alberto Contreras-Sanz More articles by this author Peter Black More articles by this author Dirk Lange More articles by this author Expand All Advertisement PDF downloadLoading ...