Bladder cancer microbiome and its association with chemoresponse

Area of Science:

• Urology
• Microbiology
• Oncology

Background:

• The urinary microbiome's role in bladder cancer is significant but understudied.
• Understanding the urinary microbiome is crucial for cancer diagnosis and treatment.

Purpose of the Study:

• To characterize the urinary microbiome in bladder cancer patients.
• To identify microbial differences between cancerous and healthy bladders.
• To explore the microbiome's impact on chemotherapy efficacy.

Main Methods:

• Analysis of The Cancer Genome Atlas (TCGA) data and 16S rRNA sequencing of patient urine and tumor samples.
• Comparison of matched urine and tumor microbiomes.
• Induction of bladder cancer in a mouse model using N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN).
• In vitro testing of *E. coli*'s effect on gemcitabine toxicity.

Main Results:

• Enrichment of 27 viral and bacterial species in bladder tumors, including sex-specific bacteria like *Lactobacillus* and *Prevotella* in females.
• Distinct urinary microbiome profiles differentiating cancer patients from controls.
• Identification of specific bacteria associated with chemotherapy response (*Granulicatella*, *Proteus*, *E. Faecalis*).
• Significant overlap (32%) between urine and tumor microbiomes.
• Limited persistent microbial changes after antibiotic exposure.
• BBN-induced microbial changes in mice were linked to BBN exposure, not carcinogenesis.
• Gammaproteobacteria in urine from bladder cancer patients were found to detoxify gemcitabine.

Conclusions:

• Established novel associations between the urinary microbiome and bladder cancer.
• Highlighted the potential role of the microbiome in influencing cancer biology and therapeutic outcomes.
• Provided a foundation for future functional studies on the urinary microbiome in bladder cancer.