The Urinary Microbiome and Bladder Cancer: Susceptibility and Immune Responsiveness

Andolfi, Ciro; Bloodworth, Jeffrey; Papachristos, Apostolos; Sweis, Randy F.

doi:10.3233/blc-200277

Cited by 28 publications

(25 citation statements)

References 55 publications

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“…The urinary microbiome has since been implicated in UBC [16]. Studies found differences in microbe abundance between urine of healthy patients and UBC patients; however, the mechanisms of how different microbe abundances may interact with EMT and ECM-related protein expression remains unclear [16]. In this study, we correlated the abundance of intra-tumor bacteria to the expression of genes involved in MIBC EMT, including genes encoding for ECM proteins.…”

Section: Introductionmentioning

confidence: 96%

“…For decades, the urinary tract and urine were believed to be sterile. However, recent studies challenged this idea, and it is now widely accepted that the urinary tract, including the bladder, is not sterile [16]. The urinary microbiome has since been implicated in UBC [16].…”

Section: Introductionmentioning

confidence: 99%

“…However, recent studies challenged this idea, and it is now widely accepted that the urinary tract, including the bladder, is not sterile [16]. The urinary microbiome has since been implicated in UBC [16]. Studies found differences in microbe abundance between urine of healthy patients and UBC patients; however, the mechanisms of how different microbe abundances may interact with EMT and ECM-related protein expression remains unclear [16].…”

Section: Introductionmentioning

confidence: 99%

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The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

Iyangar

Reddy

et al. 2021

Cancers

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The intra-tumor microbiome has recently been linked to epithelial–mesenchymal transition (EMT) in a number of cancers. However, the relationship between EMT and microbes in bladder cancer has not been explored. In this study, we profiled the abundance of individual microbe species in the tumor samples of over 400 muscle invasive bladder carcinoma (MIBC) patients. We then correlated microbe abundance to the expression of EMT-associated genes and genes in the extracellular matrix (ECM), which are key players in EMT. We discovered that a variety of microbes, including E. coli, butyrate-producing bacterium SM4/1, and a species of Oscillatoria, were associated with expression of classical EMT-associated genes, including E-cadherin, vimentin, SNAI2, SNAI3, and TWIST1. We also found significant correlations between microbial abundance and the expression of genes in the ECM, specifically collagens and elastin. Lastly, we found that a large number of microbes exhibiting significant correlations to EMT are also associated with clinical prognosis and outcomes. We further determined that the microbes we profiled were likely not environmental contaminants. In conclusion, we discovered that the intra-tumoral microbiome could potentially play a significant role in the regulation of EMT in MIBC.

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Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

Iyangar

Reddy

et al. 2021

Cancers

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“…There is a growing number of studies investigating the microbiome in benign urological conditions,15–20 but only a few studies to date have explored the role of the urinary microbiome in urological malignancies 21–25. Xu et al showed that Streptococcus abundance was significantly elevated in urine specimen from urothelial carcinoma patients compared with healthy individuals 21.…”

Section: Introductionmentioning

confidence: 99%

Prospective observational study of the role of the microbiome in BCG responsiveness prediction (SILENT-EMPIRE): a study protocol

et al. 2022

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IntroductionThe human microbiota, the community of micro-organisms in different cavities, has been increasingly linked with inflammatory and neoplastic diseases. While investigation into the gut microbiome has been robust, the urinary microbiome has only recently been described. Investigation into the relationship between bladder cancer (BC) and the bladder and the intestinal microbiome may elucidate a pathophysiological relationship between the two. The bladder or the intestinal microbiome or the interplay between both may also act as a non-invasive biomarker for tumour behaviour. While these associations have not yet been fully investigated, urologists have been manipulating the bladder microbiome for treatment of BC for more than 40 years, treating high grade non-muscle invasive BC (NMIBC) with intravesical BCG immunotherapy. Neither the association between the microbiome sampled directly from bladder tissue and the response to BCG-therapy nor the association between response to BCG-therapy with the faecal microbiome has been studied until now. A prognostic tool prior to initiation of BCG-therapy is still needed.Methods and analysisIn patients with NMIBC bladder samples will be collected during surgery (bladder microbiome assessment), faecal samples (microbiome assessment), instrumented urine and blood samples (biobank) will also be taken. We will analyse the microbial community by 16S rDNA gene amplicon sequencing. The difference in alpha diversity (diversity of species within each sample) and beta diversity (change in species diversity) between BCG-candidates will be assessed. Subgroup analysis will be performed which will lead to the development of a clinical prediction model estimating risk of BCG-response.Ethics and disseminationThe study has been approved by the Cantonal Ethics Committee Zurich (2021-01783) and it is being conducted in accordance with the Declaration of Helsinki and Good Clinical Practice. Study results will be disseminated through peer-reviewed journals and national and international scientific conferences.Trial registration numberNCT05204199.

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“…Especially important is gut microbiota, whose disruption can lead to cancer generation by promotion of chronic inflammation, alteration of normal metabolism, genotoxicity, and weakening of the immune response ( 4 ). The microbiome is also present in the urinary tract, which for a long time was considered sterile ( 6 ). Recent studies have shown that modulation of the microbiome can improve therapeutic response to immune checkpoint inhibitors, which can influence the effectiveness of immunotherapy in cancer treatment ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Quinolones as a Potential Drug in Genitourinary Cancer Treatment—A Literature Review

et al. 2022

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Quinolones, broad-spectrum antibiotics, are frequently prescribed by urologists for many urological disorders. The mechanism of their bactericidal activity is based on the inhibition of topoisomerase II or IV complex with DNA, which consequently leads to cell death. It has been observed that these antibiotics also act against the analogous enzymes present in eukaryotic cells. Due to their higher accumulation in urine and prostate tissue than in serum, these drugs seem to be ideal candidates for application in genitourinary cancer treatment. In this study, an extensive literature review has been performed to collect information about concentrations achievable in urine and prostate tissue together with information about anticancer properties of 15 quinolones. Special attention was paid to the application of cytotoxic properties of quinolones for bladder and prostate cancer cell lines. Data available in the literature showed promising properties of quinolones, especially in the case of urinary bladder cancer treatment. In the case of prostate cancer, due to low concentrations of quinolones achievable in prostate tissue, combination therapy with other chemotherapeutics or another method of drug administration is necessary.

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The Urinary Microbiome and Bladder Cancer: Susceptibility and Immune Responsiveness

Cited by 28 publications

References 55 publications

The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

The Bladder Microbiome Is Associated with Epithelial–Mesenchymal Transition in Muscle Invasive Urothelial Bladder Carcinoma

Prospective observational study of the role of the microbiome in BCG responsiveness prediction (SILENT-EMPIRE): a study protocol

Quinolones as a Potential Drug in Genitourinary Cancer Treatment—A Literature Review

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