Microbiome and bladder cancer

The microbiome has gained increasing momentum in cancer research, as it has become clear that microorganisms residing within our body are involved in mediating the cellular and tissue metabolism in health and disease. In bladder cancer research, there are different microbial communities that may mediate cancer pathobiology and response to therapy: the gut microbiome, the urinary microbiome, the urothelium-bound microbiome. These bacterial communities may mediate the processes of carcinogenesis or recurrence, modify the response to local intravesical therapies or influence the activity of systemic anticancer protocols. Based on these premises, my research project aimed to unveil the urinary and urothelium-bound microbiome in therapy-naïve bladder cancer patients, describing the differently enriched bacterial communities using a sex-based stratification. Compared to healthy controls, I found that the urine of men affected by bladder cancer were enriched in the order Opitutales and subordinate family Opitutaceae, together with the isolated class Acidobacteria-6, while in female patients I found enriched the genus Klebsiella. Notably, the bladder cancer tissue was enriched in the genus Burkholderia in both men and women, when compared to non-neoplastic, paired urothelium biopsies. Then, I also characterized the gut microbiome of bladder cancer patients undergoing neoadjuvant pembrolizumab to understand if the intestinal bacteria may influence the immune-mediated anticancer activity. In this set, I have reported that antibiotic therapy has a negative effect on immunotherapy efficacy. Second, the gut microbiome of patients not responding to neoadjuvant pembrolizumab was characterized by a higher abundance of Ruminococcus bromii, while patients who showed a response were enriched in the genus Sutterella. Lastly, I started the implementation of in vivo and in vitro systems to test the mechanistic role of the bacteria identified in human samples. This thesis work reported innovative data on the role of different microbial communities (urinary/urothelium-bound/fecal) in bladder cancer and bladder cancer therapy, and provided novel in vivo and in vitro models to validate those finding and uncover the complex microbiome-host cells crosstalk in bladder cancer patients.