Profiling the Bladder Microbiota in Patients With Bladder Cancer

Abstract

Evidence suggests that microbiota may contribute to the pathogenesis of several diseases, including cancer. In the case of bladder cancer, preliminary studies have found alterations in the urinary microbiota of patients with urothelial carcinoma compared with healthy individuals. Conversely, the urinary microbiota differ between men and women, and it has been hypothesized that these differences are associated with the lower incidence of bladder cancers in women. The objective of this study was to characterize the bladder microbiota in paired samples of tumor and non-tumor mucosa of patients with malignant bladder neoplasia using next-generation sequencing. In addition, we aimed to study potential differences in microbial composition in tumor samples according to clinical and pathological variables, and to determine possible microbial profiles. We found significant differences in microbial richness at the genus level, with a higher richness observed in the non-tumor compared with the tumor mucosa. It was also shown that Actinobacteria were significantly more enriched in the non-tumor compared with the tumor mucosa (P = 0.014). In the multivariate analysis, we found significant differences in microbial composition according to tumor grade (P = 0.03 and 0.04 at the phylum and genus levels, respectively). Moreover, we detected a higher microbial richness in non-tumor vs. tumor tissues which agrees with the global assumption that microbial richness is an indicator of health. The greater abundance of members of the Actinobacteria phylum in the non-neoplastic bladder mucosa samples supports the hypothesis that a higher abundance of Actinomycetes is associated with a lower rate of bladder cancer in women and suggests a protective role for these microbiota. We detected a microbial profile that was enriched for Enterococcus in low-grade tumors. Finally, we identified the presence of two clusters in the microbial composition of the tumor mucosa samples, significantly enriched for the genera Barnesiella, Parabacteroides, Prevotella, Alistipes, and Lachnospiracea_incertae_sedis (Cluster 1), or Staphylococcus (Cluster 2). Further longitudinal studies are needed to assess the role of the bladder microbiota in carcinogenesis.

Possibilities and limitations of using low biomass samples for urologic disease and microbiome research

“…Parra-Grande et al have reported that the amount of Actinobacteria is much higher in non-neoplastic bladder mucosa specimens than in tumor tissues, 45 supporting the hypothesis that Actinomycete -rich microbes associated with a lower incidence of BCa in women might have a preventive effect against BCa. Pederzoli et al 46 have demonstrated noticeable cluster differences in urine and tissue samples between males and females, implicating intersexual differences in microbiome that may explain the reduced prevalence of BCa in females due to the overall bladder microenvironment.…”

“…Using urine samples (urination and catheterization/cystoscopy), some studies have reported significantly greater α and β diversities. 45 , 56 However, Chipollini et al 57 have demonstrated lower α diversity in BCa compared to matched healthy controls. Wu et al 58 and Zeng et al 59 have shown that richness measures of males with BCa are higher than those of males without cancer.…”

“…These can be broadly classified into studies using urine samples and studies using tissues. Using tissue samples, Liu et al 50 and Parra-Grande et al 45 have analyzed the microbiome of patients with bladder tumor study and found a relative decrease in species by α-diversity in tumor tissues compared to that in non-malignant tissues. Bladder microbiome abundances of phyla such as Firmicutes and Actinobacteria were similar to urinary microbiome values of previous studies.…”

Tumor microbiome – an integral part of the tumor microenvironment

“…Interestingly, a higher abundance of Enterococcus showed in low-grade tumors. Based on these findings, detected microorganisms might play a role in the initial development of bladder cancer ( 170 ). Mansour et al.…”

Research progress on the microbiota in bladder cancer tumors

“…observed a significantly greater abundance of Actinobacteria in nonneoplastic bladder mucosa than in tumor tissues (P = 0.014). Although not statistically significant at the genus level, Propionibacterium was more abundant in the non-tumor mucosa (P = 0.08) ( Parra-Grande et al., 2022 ). Propionibacterium freudenreichii , notable for its probiotic potential and commercial relevance, has been suggested to be a protective agent against colorectal cancer.…”