The Role of the Urinary and Gut Microbiome in Bladder Cancer: Emerging Insights and Clinical Implications

Bladder cancer (BCa) arises from the interaction between environmental exposures and the host’s immunity and microbiome. Once considered sterile, the urinary tract is now known to harbor a resident urinary microbiome (UM) that dynamically interacts with the immune system and is influenced by systemic immunomodulatory effects of the gut microbiome (GM) brought on by the emerging gut–bladder axis. Accumulating evidence links alterations in UM and GM leading to BCa development, progression, and recurrence. Loss of protective taxa (e.g., Lactobacillus, Bifidobacterium and Ruminococcus) and enrichment of pro-inflammatory or genotoxic bacteria (e.g., Fusobacterium, Acinetobacter, Prevotella and Enterobacteriaceae) are associated with immune evasion and systemic inflammation. Microbial metabolites, especially short-chain fatty acids (SCFAs), play a key role in shaping tumor immunity and show diagnostic and prognostic potential, with specific microbial signatures correlating with recurrence risk, survival, and treatment response. Therapeutically, growing evidence suggests that microbiome composition influences immunotherapy response, highlighting opportunities for microbiome-based interventions. This review aims to summarize the rationale to implement microbial modulation strategies (e.g., dietary modulation, probiotics, fecal microbiota transplantation (FMT), and emerging synbiotic or postbiotic approaches) while addressing their current limitations and future requirements in order to develop microbiome-guided therapies, diagnostics and prognostic tools for BCa.