Global Meta-Analysis of Urine Microbiome: Colonization of PAH-Degrading Bacteria Among Bladder Cancer Patients

Despite the extensive published evidence substantiating the correlation between disease and microbiome composition, the clinical implications of these correlations and their reproducibility across diverse cohorts remain unexamined. The divergence from a "normal" microbiome, known as dysbiosis, is postulated to not only precipitate disease but has been shown to produce a suboptimal clinical response to treatment; however, this phenomenon is inadequately characterized with regard to temporal, geographical, and pathological dimensions, particularly in bladder cancer.

In our study titled "Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria among Bladder Cancer Patients," published in European Urology Oncology, our objective was to delineate the urinary microbiome in bladder cancer patients globally, in comparison with non-cancer controls, and to scrutinize the confounding influences of environmental factors versus genuine associations with the disease.¹ Our cohort comprised 129 bladder cancer patients and 60 non-cancer controls spanning four countries and three continents. We identified 97 out of 548 genera as differentially abundant in the bladder cancer urine microbiome relative to healthy patients. Nevertheless, the majority of taxonomic differences in our investigation were ascribed to collection methodologies (voided versus catheterized). We observed a significant contamination effect in countries employing voided urine (China and Croatia) compared to those utilizing catheterized samples (Hungary and the United States). However, eliminating contaminants and using catheterized specimens solely elevated the machine-learning discrimination capacity to detect bladder cancer from 0.577 to 0.995. Moreover, upon removing contaminants linked with voided urine, our study unveiled an increased abundance of polycyclic aromatic hydrocarbon (PAH)-degrading bacteria, such as Sphingomonas, Acinetobacter, Micrococcus, Pseudomonas, and Ralstonia, consistently present in bladder cancer patients.

Given that a considerable number of the bladder cancer patients examined were current or former smokers, we postulated that the presence of PAHs could establish a unique metabolic niche and furnish essential metabolic resources that facilitate the growth of specific bacteria in an environment where others cannot thrive.² The metabolic processing of PAHs by these bacteria does in fact generate more carcinogenic intermediates, (Figure 1) thereby constituting a crucial area for further investigation. Albeit our investigation primarily functions as a foundation for hypothesis generation, it presents the first global evaluation of the urinary microbiome and elucidates the biological underpinnings of smoking-related treatment failure and disease progression in bladder cancer.

Figure 1: Adapted from European Urology Jubber I, Ong S, Bukavina L. “Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors”

Written by; Emma Helstrom,³ Ilaha Isali,^1,2 Philip Abbosh,³ Laura Bukavina³

Case Western Reserve School of Medicine, Cleveland, OH
Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA.
Department of Urology, Fox Chase Cancer Center, Philadelphia, PA, USA.

References:

Bukavina L, Isali I, Ginwala R, Sindhani M, Calaway A, Magee D, Miron B, Correa A, Kutikov A, Zibelman M, Ghannoum M, Retuerto M, Ponsky L, Markt S, Uzzo R, Abbosh P. Global Meta-analysis of Urine Microbiome: Colonization of Polycyclic Aromatic Hydrocarbon-degrading Bacteria Among Bladder Cancer Patients. Eur Urol Oncol. 2023 Apr;6(2):190-203. Epub 2023 Mar 1. PMID: 36868921.
I. Jubber, S. Ong, L. Bukavina et al., Epidemiology of Bladder Cancer in 2023: A Systematic Review of Risk Factors, Eur Urol. (2023), https://doi.org/10.1016/j.eururo.2023.03.029

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