Skip to main content
SpringerLink
Log in

The Gut and Urinary Microbiota: A Rising Biomarker in Genitourinary Malignancies

  • Chapter
  • First Online:
Neoadjuvant Immunotherapy Treatment of Localized Genitourinary Cancers

  • 471 Accesses

Abstract

The homeostasis and function of each human organ are associated with site-specific microbial communities (i.e., the microbiome). More importantly, microbial genes greatly outweigh human genes, indicating a profound influence by microbial communities and microbial metabolites on organ function, as well as hormone synthesis and xenobiotic turnover. Primarily for the gut-resident microbiome, several reports have associated dysbiosis (i.e., perturbance of the homeostatic microbiome) with the onset and progression of diseases, including several solid tumors, and with the efficacy of chemotherapy and immunotherapy. It is clear from these premises that the microbiome plays a central role in the management of cancer patients, including those with genitourinary neoplasias. In this chapter, we will review the current evidence of the contribution of the microbiome to tumor development and treatment in the genitourinary system.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Nejman D, et al. The human tumor microbiome is composed of tumor type–specific intracellular bacteria. Science. 2020;368:973–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. MacCarthy-Morrogh L, Martin P. The hallmarks of cancer are also the hallmarks of wound healing. Sci Signal. 2020;13:eaay8690.

    CAS  PubMed  Google Scholar 

  3. Amieva M, Peek RM. Pathobiology of helicobacter pylori–induced gastric cancer. Gastroenterology. 2016;150:64–78.

    CAS  PubMed  Google Scholar 

  4. Babjuk M, et al. EAU guidelines on non-muscle-invasive bladder cancer (TaT1 and CIS) 2020. in European Association of Urology Guidelines. 2020 Edition vol. presented at the EAU Annual Congress Amsterdam 2020 (European Association of Urology Guidelines Office, 2020).

    Google Scholar 

  5. Peppercorn MA, Goldman P. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther. 1972;181:555–62.

    CAS  PubMed  Google Scholar 

  6. Spanogiannopoulos P, Bess EN, Carmody RN, Turnbaugh PJ. The microbial pharmacists within us: a metagenomic view of xenobiotic metabolism. Nat Rev Microbiol. 2016;14:273–87.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Koppel N, Rekdal VM, Balskus EP. Chemical transformation of xenobiotics by the human gut microbiota. Science. 2017;356:eaag2770.

    PubMed  Google Scholar 

  8. Alexander JL, et al. Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14:356–65.

    CAS  PubMed  Google Scholar 

  9. Sivan A, et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350:1084–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Wallace BD, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330:831–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Paramsothy S, et al. Multidonor intensive faecal microbiota transplantation for active ulcerative colitis: a randomised placebo-controlled trial. Lancet. 2017;389:1218–28.

    PubMed  Google Scholar 

  12. Bhatt AP, Redinbo MR, Bultman SJ. The role of the microbiome in cancer development and therapy. CA Cancer J Clin. 2017;67:326–44.

    PubMed  PubMed Central  Google Scholar 

  13. Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25:377–88.

    CAS  PubMed  Google Scholar 

  14. Gopalakrishnan V, Helmink BA, Spencer CN, Reuben A, Wargo JA. The influence of the gut microbiome on cancer, immunity, and cancer immunotherapy. Cancer Cell. 2018;33:570–80.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wang F, Meng W, Wang B, Qiao L. Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett. 2014;345:196–202.

    CAS  PubMed  Google Scholar 

  16. Tsilimigras MCB, Fodor A, Jobin C. Carcinogenesis and therapeutics: the microbiota perspective. Nat Microbiol. 2017;2:17008.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Garrett WS. Cancer and the microbiota. Science. 2015;348:80–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Nakatsu G, et al. Gut mucosal microbiome across stages of colorectal carcinogenesis. Nat Commun. 2015;6:8727.

    CAS  PubMed  Google Scholar 

  19. Geller LT, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357:1156–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Gopalakrishnan V, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359:97–103.

    CAS  PubMed  Google Scholar 

  21. Viaud S, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342:971–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Iida N, et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342:967–70.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Vétizou M, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350:1079–84.

    PubMed  PubMed Central  Google Scholar 

  24. Routy B, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359:91–7.

    CAS  PubMed  Google Scholar 

  25. Matson V, et al. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Science. 2018;359:104–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Ma W, et al. Gut microbiota shapes the efficiency of cancer therapy. Front Microbiol. 2019;10:1050.

    PubMed  PubMed Central  Google Scholar 

  27. Chaput N, et al. Baseline gut microbiota predicts clinical response and colitis in metastatic melanoma patients treated with ipilimumab. Ann Oncol. 2017;28:1368–79.

    CAS  PubMed  Google Scholar 

  28. Dubin K, et al. Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis. Nat Commun. 2016;7:10391.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Hershman DL, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32:1941–67.

    CAS  PubMed  Google Scholar 

  30. Shen S, et al. Gut microbiota is critical for the induction of chemotherapy-induced pain. Nat Neurosci. 2017;20:1213–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Yu T, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170:548–563.e16.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Gur C, et al. Binding of the Fap2 protein of fusobacterium nucleatum to human inhibitory receptor TIGIT protects tumors from immune cell attack. Immunity. 2015;42:344–55.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Zheng JH, et al. Two-step enhanced cancer immunotherapy with engineered Salmonella typhimurium secreting heterologous flagellin. Sci Transl Med. 2017;9:eaak9537.

    PubMed  Google Scholar 

  34. Roberts W. On the occurrence of micro-organisms in fresh urine. Br Med J. 1881;2:623–5.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Maskell R, Pead L, Allen J. The puzzle of ‘urethral syndrome’: a possible answer? Lancet. 1979;1:1058–9.

    CAS  PubMed  Google Scholar 

  36. Bajic P, et al. Male bladder microbiome relates to lower urinary tract symptoms. Eur Urol Focus. 2020;6:376–82.

    PubMed  Google Scholar 

  37. Wolfe AJ, et al. Evidence of uncultivated bacteria in the adult female bladder. J Clin Microbiol. 2012;50:1376–83.

    PubMed  PubMed Central  Google Scholar 

  38. Pederzoli F, et al. Sex-specific alterations in the urinary and tissue microbiome in therapy-naïve urothelial bladder cancer patients. Eur Urol Oncol. 2020;3:784–8.

    Google Scholar 

  39. Hilt EE, et al. Urine is not sterile: use of enhanced urine culture techniques to detect resident bacterial flora in the adult female bladder. J Clin Microbiol. 2014;52:871–6.

    PubMed  PubMed Central  Google Scholar 

  40. Derosa L, et al. Gut bacteria composition drives primary resistance to cancer immunotherapy in renal cell carcinoma patients. Eur Urol. 2020;78:195–206.

    CAS  PubMed  Google Scholar 

  41. Salgia NJ, et al. Stool microbiome profiling of patients with metastatic renal cell carcinoma receiving anti–PD-1 immune checkpoint inhibitors. Eur Urol. 2020;78:498–502.

    CAS  PubMed  Google Scholar 

  42. Pal SK, et al. Stool bacteriomic profiling in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor–tyrosine kinase inhibitors. Clin Cancer Res. 2015;21:5286–93.

    CAS  PubMed  Google Scholar 

  43. Hahn AW, et al. Targeting bacteroides in stool microbiome and response to treatment with first-line VEGF tyrosine kinase inhibitors in metastatic renal-cell carcinoma. Clin Genitourin Cancer. 2018;16:365–8.

    PubMed  Google Scholar 

  44. Dennis LK, Lynch CF, Torner JC. Epidemiologic association between prostatitis and prostate cancer. Urology. 2002;60:78–83.

    PubMed  Google Scholar 

  45. Roberts RO, Bergstralh EJ, Bass SE, Lieber MM, Jacobsen SJ. Prostatitis as a risk factor for prostate cancer. Epidemiology. 2004;15:93–9.

    PubMed  Google Scholar 

  46. Cheng I, et al. Prostatitis, sexually transmitted diseases, and prostate cancer: the California men’s health study. PLoS One. 2010;5:e8736.

    PubMed  PubMed Central  Google Scholar 

  47. Sutcliffe S, et al. Gonorrhea, syphilis, clinical prostatitis, and the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 2006;15:2160–6.

    PubMed  Google Scholar 

  48. Hochreiter WW, Duncan JL, Schaeffer AJ. Evaluation of the bacterial flora of the prostate using a 16S rRNA gene based polymerase chain reaction. J Urol. 2000;163:127–30.

    CAS  PubMed  Google Scholar 

  49. Cavarretta I, et al. The microbiome of the prostate tumor microenvironment. Eur Urol. 2017;72:625–31.

    CAS  PubMed  Google Scholar 

  50. Yow MA, et al. Characterisation of microbial communities within aggressive prostate cancer tissues. Infect Agents Cancer. 2017;12:4.

    Google Scholar 

  51. Sfanos KS, et al. A molecular analysis of prokaryotic and viral DNA sequences in prostate tissue from patients with prostate cancer indicates the presence of multiple and diverse microorganisms. Prostate. 2008;68:306–20.

    CAS  PubMed  Google Scholar 

  52. Shrestha E, et al. Oncogenic Gene Fusions in Non-Neoplastic Precursors as Evidence that Bacterial Infection Initiates Prostate Cancer. bioRxiv 2020.07.27.224154. 2020. https://doi.org/10.1101/2020.07.27.224154.

  53. Mani RS, et al. Inflammation induced oxidative stress mediates gene fusion formation in prostate cancer. Cell Rep. 2016;17:2620–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Pederzoli F, et al. Targetable gene fusions and aberrations in genitourinary oncology. Nat Rev Urol. 2020. https://doi.org/10.1038/s41585-020-00379-4.

  55. Shoskes DA, et al. The urinary microbiome differs significantly between patients with chronic prostatitis/chronic pelvic pain syndrome and controls as well as between patients with different clinical phenotypes. Urology. 2016;92:26–32.

    PubMed  Google Scholar 

  56. Shrestha E, et al. Profiling the urinary microbiome in men with positive versus negative biopsies for prostate cancer. J Urol. 2018;199:161–71.

    PubMed  Google Scholar 

  57. Shin J-H, et al. Serum level of sex steroid hormone is associated with diversity and profiles of human gut microbiome. Res Microbiol. 2019;170:192–201.

    CAS  PubMed  Google Scholar 

  58. Ridlon JM, et al. Clostridium scindens: a human gut microbe with a high potential to convert glucocorticoids into androgens. J Lipid Res. 2013;54:2437–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Harada N, et al. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice. Sci Rep. 2016;6:23001.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sfanos KS, et al. Compositional differences in gastrointestinal microbiota in prostate cancer patients treated with androgen axis-targeted therapies. Prostate Cancer Prostatic Dis. 2018;21:539–48.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Chipollini J, et al. Characterization of urinary microbiome in patients with bladder cancer: results from a single-institution, feasibility study. Urol Oncol. 2020;38:615–21.

    CAS  PubMed  Google Scholar 

  62. Wu P, et al. Profiling the urinary microbiota in male patients with bladder cancer in China. Front Cell Infect Microbiol. 2018;8:167.

    PubMed  PubMed Central  Google Scholar 

  63. Bučević Popović V, et al. The urinary microbiome associated with bladder cancer. Sci Rep. 2018;8:12157.

    PubMed  PubMed Central  Google Scholar 

  64. Mai G, et al. Common core bacterial biomarkers of bladder cancer based on multiple datasets. Biomed Res Int. 2019;2019:4824909.

    PubMed  PubMed Central  Google Scholar 

  65. Tannenbaum C, Ellis RP, Eyssel F, Zou J, Schiebinger L. Sex and gender analysis improves science and engineering. Nature. 2019;575:137–46.

    CAS  PubMed  Google Scholar 

  66. Koti M, et al. Sex differences in bladder cancer immunobiology and outcomes: a collaborative review with implications for treatment. Eur Urol Oncol. S2588931120301401. 2020. https://doi.org/10.1016/j.euo.2020.08.013.

  67. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116:180–2.

    CAS  PubMed  Google Scholar 

  68. Pettenati C, Ingersoll MA. Mechanisms of BCG immunotherapy and its outlook for bladder cancer. Nat Rev Urol. 2018;15:615–25.

    CAS  PubMed  Google Scholar 

  69. Bandini M, et al. Does the administration of preoperative pembrolizumab lead to sustained remission post-cystectomy? First survival outcomes from the PURE-01 study. Ann Oncol. 2020;31:1755–63.

    CAS  PubMed  Google Scholar 

  70. Pederzoli F, et al. Neoadjuvant chemotherapy or immunotherapy for clinical T2N0 muscle-invasive bladder cancer: time to change the paradigm? Eur Urol Oncol. 2020.

    Google Scholar 

  71. Powles T, et al. Clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial. Nat Med. 2019;25:1706–14.

    CAS  PubMed  Google Scholar 

  72. Alfano M, Pederzoli F, Bandini M, Necchi A. The new era of precision urobiome: RE: ‘characterization of urinary microbiome in patients with bladder cancer: results from a single-institution, feasibility study’ by Chipollini et al. Urol Oncol. 2020;38:693–4.

    PubMed  Google Scholar 

  73. Bandini M, et al. Modeling 1-year relapse-free survival after neoadjuvant chemotherapy and radical cystectomy in patients with clinical T2-4N0M0 urothelial bladder carcinoma: endpoints for phase 2 trials. Eur Urol Oncol. 2019;2:248–56.

    PubMed  Google Scholar 

  74. Pederzoli F, et al. Incremental utility of adjuvant chemotherapy in muscle-invasive bladder cancer: quantifying the relapse risk associated with therapeutic effect. Eur Urol. 2019;76:425–9.

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Experimental Oncology/Unit of Urology, Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy

    Filippo Pederzoli, Valentina Murdica, Andrea Salonia & Massimo Alfano

  2. Vita-Salute San Raffaele University, Milan, Italy

    Filippo Pederzoli & Andrea Salonia

Authors
  1. Filippo Pederzoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Valentina Murdica
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrea Salonia
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Massimo Alfano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Massimo Alfano .

Editor information

Editors and Affiliations

  1. Medical Oncology and Urology, Vita-Salute San Raffaele University, Milano, Milano, Italy

    Andrea Necchi

  2. Department of Genitourinary Oncology, University of South Florida, Tampa, FL, USA

    Philippe E. Spiess

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pederzoli, F., Murdica, V., Salonia, A., Alfano, M. (2022). The Gut and Urinary Microbiota: A Rising Biomarker in Genitourinary Malignancies. In: Necchi, A., Spiess, P.E. (eds) Neoadjuvant Immunotherapy Treatment of Localized Genitourinary Cancers. Springer, Cham. https://doi.org/10.1007/978-3-030-80546-3_19

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-80546-3_19

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-80545-6

  • Online ISBN: 978-3-030-80546-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation