AUA 2020: John K. Lattimer Lecture: The Urinary Microbiome Impacts Urologic Disease

(UroToday.com) The John K. Lattimer Lecture at the 2020 American Urologic Association (AUA) Virtual Annual Meeting was provided by J. Curtis Nickel, MD, discussing the impact of the urinary microbiome on urologic disease. Dr. Nickel notes that the traditional dogma is that the urinary tract is normally sterile, a belief that has persisted until the last decade. Interestingly, when the Human Microbiome Project was undertaken (2007-2016), the urinary tract was not included. Dr. Nickel notes that since then, increased utilization of next-generation sequencing has improved and changed our understanding of microbes. Not surprisingly, the urinary tract is not sterile and has been described as a “veritable microbial jungle”, including 330 bacterial previously identified in the urinary tract.1

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In fact, these initial estimates of the bladder microbiome are not even close. In >70,000 urine samples collection, >4,000 species of bacteria were identified, including E. coli being predominant in 28% of samples. As such, Dr. Nickel notes that the urinary tract is complicated, wherein the microbiota of different sites are often very different, depending on how/where the urine was collected: (i) voided urine, (ii) catheterized urine, (iii) urethra, (iv) peri-urethra.

Dr. Nickel notes that the microbiome has been implicated in urologic chronic pelvic pain, including interstitial cystitis/bladder pain syndrome, and chronic prostatitis/chronic pelvic pain syndrome. In a study from Dr. Nickel’s group, among 110 men with chronic prostatitis/chronic pelvic pain syndrome and 115 asymptomatic controls, there were 78 bacterial species identified (48 genera total), with the most common organism Burkholderia cenocepacia. Similarly, among 181 women with interstitial cystitis/female bladder pain syndrome and 182 asymptomatic controls, there were 97 bacterial species identified (41 genera total), with the most common organism Lactobacillus gasseri.

There is also a link between bladder microbiota and female lower urinary tract symptoms. This includes urgency urinary incontinence, responses to overactive bladder, post instrumentation, and post-surgical UTIs. Additionally, the connection between bacterial infection and the formation of kidney stones has been long-standing. Specifically, there is an inverse relationship between intestinal colonization with Oxalobacter formigenes and the development of calcium oxalate stones; colonization with O. formigenes was associated with a 70% reduction in urolithiasis risk.2 Dr. Nickel notes that there is a combination of dysbiosis in urinary stone disease, whereby the gut has a loss of oxalate metabolism and there is a shift from Prevotella to Enterobacteriaceae. In the urinary tract, a shift also occurs form Lactobacillus to Enterobacteriaceae, resulting in stones dominated by Enterobacteriaceae.

Urinary cancer and the microbiome also share a relationship. Cancer development and progression are impacted by an interplay between normal and tumor cells with the extracellular environment, bacteria, and bacterial products control tissue homeostasis and inflammation, long term dysregulation caused by dysbiosis may result in a pro-tumorigenic environment, which eventually leads to urologic malignancy. Specific to bladder cancer, the urinary microbiome pattern was found to be more hostile among those with frequent recurrences compared to those with no recurrence, and the urinary microbiome pattern has been associated with clinical response to Bacillus Calmette-Guerin (BCG) intravesical therapy. With regards to prostate cancer, the situation is more complicated as several studies have assessed the relationship of microbiota and development of disease.

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Dr. Nickel notes that there are ways to manipulate our urinary microbiome, including through diet, exercise, avoiding environmental pollution, and avoiding antibiotics. This may be particularly important when considering manipulating our microbiome for cancer management, including (i) promoting a “healthy” anti-tumorigenic microbiome, (ii) finding microbiota-based markers for cancer risk or detection, (iii) determining microbiota that enhances treatment success, and (iv) targeting microbiota which may bypass treatment resistance mechanisms of tumor cells. 

Presented by: J. Curtis Nickel, MD, FRCSC Professor of Urology, Queen's University, Tier 1 Canada Research Chair in Urologic Pain and Inflammation Kingston General Hospital Kingston, Ontario, Canada

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia at the 2020 American Urological Association (AUA) Annual Meeting, Virtual Experience #AUA20, June 27- 28, 2020

References:

  1. Morand A, Cornu F, Dufour JC, et al. Human Bacterial Repertoire of the Urinary Tract: A Potential Paradigm Shift. J Clin Microbiol 2019 Feb 27;57(3):e00675-18.
  2. Aragon IM, Herrera-Imbroda B, Queipo-Ortuno M, et al. The Urinary Tract Microbiome in Health and Disease. Eur Urol Focus 2018 Jan;4(1):128-138.
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