2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Bladder Cancer

Sex-Specific Alterations in the Urinary and Tissue Microbiome in Therapy-Naïve Urothelial Bladder Cancer Patients - Beyond the Abstract

The study of the role of the microbiome in cancer research has gained increasing interest over the last years, as it appears to play a central role from tumorigenesis to response to treatment, including a major regulation of the response to immunotherapy treatments.1–3 A bidirectional interplay between the microbiome and sex hormones has been reported,4,5 and this interplay may explain, at least in part, the sex-based differences in bladder cancer pathobiology.6 The urinary microbiome represents a promising candidate in the field of predictive and prognostic biomarkers, due to the non-invasiveness and the easiness of collection. However, a description of the microbial communities present in the bladder cancer tissue has not been clearly reported, a description that is important to understand how the microbiome could contribute to the urothelial transformation through chronic inflammation, the release of genotoxic factors, or other mechanisms.7 Moreover, the relationship between bladder tissue and urine microbial communities has not been clearly elucidated so far in the context of bladder cancer.  



In this framework, we characterized the urinary and bladder tissue microbial communities in therapy-naïve bladder cancer patients, to study the gender-specific microbiome differences in bladder cancer. We have established the gender-specific urinary microbiome of bladder cancer patients, and by comparing paired neoplastic bladder, non-neoplastic tissues and urines of bladder cancer patients, we introduced for the first time the concept of sex-specific “shared bladder microbiome” between urine and bladder tissue.8

Using a total of 166 specimens collected from bladder cancer patients and healthy controls, we found that, at the tissue level, the genus Burkholderia was enriched in the neoplastic vs. the non-neoplastic bladder tissue in both genders. The higher abundance of the genus Burkholderia was previously reported in colorectal cancer9 and it has been reported in association response to immunotherapy.2

In the urine of male patients, when compared to controls, we did not identify any enriched taxa, whereas enrichment of the genus Klebsiella was identified in the urine of female patients.

These findings are relevant to design and interpret future studies exploiting the urinary microbiome as a potential proxy of the tissue microenvironment. The data from treatment-naïve patients also constitute a first step toward understanding thoroughly the influence of the bladder microbiome on therapy against bladder cancer. We may envision a near future in which the presence of specific bacterial taxa in the genitourinary system could predict therapy efficacy, and we might be able to manipulate the urinary microbiome to improve patient outcomes. The translational research involving the microbiome and bladder cancer is still at the beginning.

Written by: Massimo Alfano, MSc, PhD,1 Filippo Pederzoli, MD, PhD,1,2 Andrea Salonia, MD1,2

  1. Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy 
  2. Vita-Salute San Raffaele University, Milan, Italy
References:

  1. Helmink, Beth A., MA Wadud Khan, Amanda Hermann, Vancheswaran Gopalakrishnan, and Jennifer A. Wargo. "The microbiome, cancer, and cancer therapy." Nature medicine 25, no. 3 (2019): 377-388.
  2. Vétizou, Marie, Jonathan M. Pitt, Romain Daillère, Patricia Lepage, Nadine Waldschmitt, Caroline Flament, Sylvie Rusakiewicz et al. "Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota." Science 350, no. 6264 (2015): 1079-1084.
  3. Gopalakrishnan, Vancheswaran, Christine N. Spencer, Luigi Nezi, Alexandre Reuben, M. C. Andrews, T. V. Karpinets, P. A. Prieto et al. "Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients." Science 359, no. 6371 (2018): 97-103.
  4. Clarke, Gerard, Roman M. Stilling, Paul J. Kennedy, Catherine Stanton, John F. Cryan, and Timothy G. Dinan. "Minireview: gut microbiota: the neglected endocrine organ." Molecular endocrinology 28, no. 8 (2014): 1221-1238.
  5. Neuman, Hadar, Justine W. Debelius, Rob Knight, and Omry Koren. "Microbial endocrinology: the interplay between the microbiota and the endocrine system." FEMS microbiology reviews 39, no. 4 (2015): 509-521.
  6. Dobruch, Jakub, Siamak Daneshmand, Margit Fisch, Yair Lotan, Aidan P. Noon, Matthew J. Resnick, Shahrokh F. Shariat, Alexandre R. Zlotta, and Stephen A. Boorjian. "Gender and bladder cancer: a collaborative review of etiology, biology, and outcomes." European urology 69, no. 2 (2016): 300-310.
  7. Alfano, Massimo, Filippo Canducci, Manuela Nebuloni, Massimo Clementi, Francesco Montorsi, and Andrea Salonia. "The interplay of extracellular matrix and microbiome in urothelial bladder cancer." Nature Reviews Urology 13, no. 2 (2016): 77.
  8. Pederzoli, Filippo, Roberto Ferrarese, Virginia Amato, Irene Locatelli, Elisa Alchera, Roberta Lucianò, Manuela Nebuloni et al. "Sex-specific Alterations in the Urinary and Tissue Microbiome in Therapy-naïve Urothelial Bladder Cancer Patients."European Urology Oncology (2020).
  9. Alomair, Ahmed O., Ibrahim Masoodi, Essam J. Alyamani, Abed A. Allehibi, Adel N. Qutub, Khalid N. Alsayari, Musaad A. Altammami, and Ali S. Alshanqeeti. "Colonic mucosal microbiota in colorectal cancer: a single-center metagenomic study in saudi arabia." Gastroenterology research and practice 2018 (2018).
Read the Abstract