Investigating the association between the urinary microbiome and bladder cancer: An exploratory study

Abstract

Introduction: We sought to investigate the association between the urinary microbiome and bladder cancer, including the difference between nonmuscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer, and Bacillus Calmette Guerin (BCG) responsive vs. BCG-refractory NMIBC.

Methods: Urine specimens were collected from consecutive patients with bladder cancer and healthy volunteers. Urine samples were analyzed using 16S rRNA sequencing to identify and compare any present bacteria. Alteration in the urinary microbiome was described in terms of alpha (diversity of populations within a sample) and beta diversities (differences between populations among different samples). Analyses were corrected for age, sex, method of sample preservation, and method of collection (mid-stream catch vs. catheterized urine).

Results: Fifty-three samples (43 patients with bladder cancer, and 10 controls) were included. For bladder cancer patients, mean age was 70 years, 7 (16%) were females; and 29 (67%) had NMIBC. Among patients with NMIBC, 11 (38%) patients received BCG, 6 of which had recurrence or progression after a median follow up of 13 months. Comparing the microbiome of bladder cancer patients vs. healthy controls, beta-diversity was significantly different, with Actinomyces, Achromobacter, Brevibacterium, and Brucella significantly more abundant in urine samples of bladder cancer patients. Comparing NMIBC and MIBC, Hemophilus and Veillonella were significantly more abundant in urine of MIBC patients, while Cupriavidus was significantly more abundant in NMIBC patients. Among NMIBC patients, Serratia and Brochothrix, Negativicoccus, Escherichia-Shigella, and Pseudomonas were significantly more abundant in patients who responded to BCG in comparison to those who did not.

Conclusion: Urinary microbiome varied between patients with bladder cancer and healthy controls. Moreover, urinary microbial profiles differed among patient with NMIBC vs. MIBC, and among BCG responsive vs. BCG refractory NMIBC.

Keywords: BCG refractory; Bladder cancer; Microbiome; Microbiota; Urinary.