Urinary microbiome according to intravesical BCG treatment
Background Recent insights reveal a urinary microbiome, challenging prior beliefs about urine's sterility. Intravesical Bacillus Calmette-Guérin (BCG) therapy is currently the most recommended treatment modality for patients with intermediate or high-risk non-muscle-invasive bladder cancer. However, the resistance rate to this therapy ranges from 30 to 50%. In cases where the malignancy progresses to a muscle-invasive status, radical cystectomy should be considered. Our research employs 16S rRNA gene sequencing to explore the role of urinary microbiome in bladder cancer (BCa) and response to BCG therapy.   Results We collected urine samples through urethral catheterization. All of the BCa patients were in the non-muscle-invasive stage and received BCG therapy, with 'Pre-BCG' samples taken at the initial surgery and 'Post-BCG' samples at follow-up cystoscopies. A total of 87 patients participated in the study, comprising 29 individuals with benign diseases and 58 BCa patients. Significant differences in bacterial compositions were observed between benign and malignant samples, suggesting toluene degradation pathway may mitigate BCa development. In post-BCG samples from responders, elevated levels of 2-oxoglutarate and L-methionine were inferred compared to their pre-BCG counterparts. Furthermore, post-BCG samples showed microbial differences in responders and increased quinolone synthesis compared to non-responders. Notably, Bifidobacterium species, particularly B. breve and B. longum, were abundant in responders, correlating with longer recurrence-free survival. We also developed a robust predictive model for malignancy and BCG response using urinary microbial composition data.  Conclusions Our study unraveled the mechanisms underlying the response to BCG treatment, focusing on the urinary microbiome and its metabolic pathways. We identified specific microbes for their potential benefits and developed clinical predictive models for malignancy and BCG therapy response.