The bladder microbiota is not significantly altered by intravesical BCG therapy

Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.