The Urinary Microbiome: A New Potential Target in Bladder Cancer Precision Medicine?

Emerging evidence has shown the impact of the microbiome on solid organ malignancies such as gastric (H. pylori) and cervical cancer (HPV). Thus, a clinically relevant question would be whether the urinary microbiome has any effect on bladder carcinogenesis and whether specific microbial profiles can help prognosticate disease outcomes. Another provocative consideration is whether its manipulation can turn patients from non-responders into responders of local therapy. Thus far, the role of microorganisms in bladder cancer pathogenesis has not been fully understood.

In our study, we extracted DNA from 37 patients for 16S ribosomal RNA sequencing. Ten patients were considered control for pairwise comparison. We found significantly decreased species richness and evenness in the urine of bladder cancer patients. We also found enrichment of unique bacterial communities for patients with invasive disease implying the existence of a specific urinary microbiome (“urobiome”) for those patients with high-risk bladder cancer.

Given the constant interaction between urine and urothelium, it is not surprising the urinary microbiome shares >80% of the bacterial families present in paired bladder tissue; thus, making the urinary microbiome a fair proxy of the urothelial bacterial environment.¹ Interestingly in our study, we found malignant urine samples to be more phylogenetically constrained than benign urine counterparts. The implication for potential predominance of unique organisms in the human bladder can be a significant consideration for future microbiome studies to target host microbial communities and provide further prognostic information for patients and providers seeking individualized treatment plans.

The human microbiome substantially interacts in various aspects of human physiology. Improvements in nucleotide sequencing technologies have allowed for the collection of diverse data sets that can now profile the human microbiome.² Our work raises the question of the potential role for the urinary microbiome and predisposition to bladder pathogenesis. Continuing the discovery of the microbiome remains extremely important. One cannot help but wonder if its manipulation can one day improve response to intravesical therapies and would need to be a focus in future urobiome research.

Written by: Juan Chipollini, MD, Assistant Professor, Department of Urology, The University of Arizona, Tucson, Arizona

References:

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).
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): 77-90.

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