The Urinary Microbiome: Implications in Bladder Cancer Pathogenesis and Therapeutics

Urine is not sterile. With the increasing use of high throughput DNA sequencing and enhanced culture techniques, investigators have just begun to scratch the surface of the urinary microbiome -- the community of commensal microorganisms residing in the urinary tract. This exciting new area of human health may have implications in various urologic disease states. While numerous associations have already been made between the urinary microbiome and benign urologic conditions, limited investigation has been performed in the realm of urologic oncology. Only a few small studies have examined the role of the urinary microbiome in bladder cancer, the second most common urological malignancy.

Based on observations from other malignancies, interactions between the urinary microbiome and the local immune microenvironment may have implications in the pathophysiology and management of bladder cancer. Interestingly, urologists have been manipulating the bladder microbiome to treat non-muscle invasive bladder cancer for over 40 years with intravesical instillations of Bacillus Calmette-Guerin (BCG) immunotherapy, an active attenuated form of Mycobacterium bovis. Presumably relying on a urothelial inflammatory response, BCG therapy is unfortunately associated with a high failure rate. Numerous investigators have attempted to predict or enhance treatment success by various means.

Based on observations from other malignancies, it is plausible that the urinary microbiome may be harnessed to enhance the diagnosis and treatment of bladder cancer. In this article, we review the history of the urinary microbiome and characterize the optimal techniques by which it should be studied. The pertinent literature relating to the urinary microbiome and bladder cancer is reviewed, and limitations of those studies are discussed. Possible roles of the urinary microbiome in bladder cancer are proposed, including its potential as a pathogenic factor, a diagnostic biomarker, or a modulator of BCG activity through competitive binding of fibronectin. The possibility of using the urinary microbiome as a therapeutic target is also discussed.

The potential impact of using the urinary microbiome to improve bladder cancer diagnosis and treatment is immense. Scientists and clinicians alike must work towards enhancing our understanding of this intriguing new area of human health.

Written by: Petar Bajic, MD, Department of Urology, Loyola University Chicago Stritch School of Medicine, Maywood, Illinois, United States

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