Microbiome-urothelium crosstalk in bladder cancer: From dysbiosis to clinical translation.

Bladder cancer (BCa) ranks among the most frequently diagnosed malignancies worldwide. The advent of high-throughput sequencing technologies has revealed distinct urinary microbial signatures that differentiate healthy individuals from BCa patients. While growing evidence implicates microbiota dysbiosis in the pathogenesis, progression, and therapeutic response of BCa, establishing a direct causal relationship remains challenging due to methodological heterogeneity across studies. This review summarizes the current knowledge of the human urinary microbiome (urobiome) in both health and disease states. It critically examines the evidence for microbiome involvement in BCa and discusses potential mechanisms, such as chronic inflammation, immune modulation, and genotoxin production, through which the microbiota may influence carcinogenesis. Furthermore, we explore the translational potential of urinary microbiota profiling as a biomarker for risk stratification and for predicting responses to intravesical therapies and immunotherapy in BCa patients. Unraveling the complexities of host-microbe interactions in BCa is essential for developing novel strategies for its prevention and personalized treatment.