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Urinary Microbiota and Urological Tumors: Where Are We Heading? - Beyond the Abstract

Yes, urine is not sterile. Ten years ago, we were quite sure that urine is a sterile environment. Multiple bacteria found in urine culture in small quantities were and are still considered as “contamination.” Yet, thanks to 16s rRNA PCR and metagenomic sequencing, it is now well-known that urine holds a wide variety of bacterial species, well-known as the “urinary microbiota”. As the gut microbiota has been clearly demonstrated to be implicated in many diseases of the gastrointestinal system as well as other systemic diseases and cancers, urinary microbiota has been implicated in numerous diseases of the urinary tract, including urge urinary incontinence in the absence of infection in women, interstitial cystitis, overactive bladder, chronic lower urinary tract symptoms, and chronic prostatitis.

Genitourinary tumors are one of these urinary tract diseases that might also be somehow related to urinary microbiota alterations, as a cause or a consequence. That means, in a way, urinary microbiota alterations might be responsible for the pathogenesis of certain tumors, or, in the other, they might be the consequence of the development of tumors in the genitourinary tract.

To our knowledge, this is the first systematic review to depict the potential role of specifically urinary microbiota in urological tumors, including bladder cancer (BCa), prostate cancer (PCa), and renal cell carcinoma (RCC).1 Most studies found were related mostly to BCa. The urine of BCa, PCa, and RCC patients presented different bacterial profiles from control patients at the different taxonomic levels. For instance, at phylum level, BCa patients were found to have more abundant levels of Proteobacteria, Firmicutes, and Actinobacteria, and at family level, BCa patients had greater amount of Burkholderiaceae, compared to control patients. The abundance and composition of urinary microbiota were also different between recurrent and non-recurrent BCa, non-muscle-invasive vs. muscle-invasive BCa, and high- vs. low-grade PCa and BCa

Since urinary microbiota is different between urological cancer patients and controls, detection of urinary microbiota alterations could be a non-invasive, non-costly, and helpful screening tool for genitourinary tumors, especially for bladder cancer and renal cell carcinoma where there is no consensus until now on screening. Moreover, like fecal immunochemical test (FIT) in gastrointestinal tumors (selecting patients for colonoscopy), urinary microbiota alterations could select patients for cystoscopy in bladder cancer, or ureteroscopy in upper tract carcinoma, and therefore play a key role in the diagnostic pathway of urothelial carcinoma. Furthermore, since these microbiota alterations have been shown to predict recurrence, they might also guide surveillance and follow-up strategies in GU cancer patients. Finally, these microbiota alterations could predict response to systemic treatment, especially immune checkpoint inhibitors, since fecal microbial transplantation (FMT), a gut microbiota modulating agent, has shown promising results in recently published studies in enhancing response to immunotherapy.2 It was demonstrated with melanoma in two proofs-of-concept studies3,4 and is now being extrapolated to urological tumors in many ongoing trials: NCT04116775 studying the effect of FMT on the efficacy of pembrolizumab in metastatic castrate resistant PCa, NCT04758507 TACITO trial studying FMT from donors responders to immunotherapy to patients with advanced RCC, etc. Other gut microbiota modulating agents such as antibiotics and proton pump inhibitors were also shown to negatively impact response to immune checkpoint inhibitors.5

Ten years ago, we were quite sure that urine is quite a sterile environment. We think that ten years from now, more knowledge of urinary microbiota could be the start of a new era in genitourinary tumors. Time, as well as prospective well-conducted studies and more standardized detection techniques, will confirm, or reject these assumptions in the near future.

Written by: Georges Mjaess MD,1 Aya Karam MD,2 Simone Albisinni MD,1 Fouad Aoun MD MSc,2 Thierry Roumeguère MD1

  1. Department of Urology, University Clinics of Brussels, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
  2. Hotel-Dieu de France, University of Saint Joseph, Faculty of Medicine, Beirut, Lebanon

References:

  1. Karam A, Mjaess G, Albisinni S, El Daccache Y, Farah M, Daou S, et al. Uncovering the role of urinary microbiota in urological tumors: a systematic review of literature. World J Urol. 2022 Jan 7
  2. Mjaess G, Karam A, Aoun F, Albisinni S, Roumeguère T. Fecal microbiota transplantation for immunotherapy-resistant urological tumors: Is it time? An update of the recent literature. Cancer. 2022 Jan 1;128(1):14–9.
  3. Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, Morrison RM, et al. Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients. Science. 2021 Feb 5;371(6529):595–602.
  4. Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021 Feb 5;371(6529):602–9.
  5. Giordan Q, Salleron J, Vallance C, Moriana C, Clement-Duchene C. Impact of Antibiotics and Proton Pump Inhibitors on Efficacy and Tolerance of Anti-PD-1 Immune Checkpoint Inhibitors. Front Immunol. 2021;12:716317.

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