The Surprising Link Between Urinary and Prostate Microbiota and Prostate Cancer

Prostate cancer is the most common cancer among men in developed countries, apart from skin cancer. More than 250 thousand men worldwide die from prostate cancer each year.

Prostate cancer has a complex / variable clinical course, and information obtained after biopsy, including the Gleason score is used to assess the likelihood of the disease being aggressive.

Predicting the Course of Cancer with Biomarkers

Identifying urinary (in the urine) biomarkers for aggressive prostate cancer is an area of growing interest. Molecules produced by the prostate gland are released into the urine. The seepage of urine into the prostate gland is well known, supporting the existence of a prostate-urine cycle.

Previously identified urinary biomarkers include gene expression profiles containing PCA3 and various gene combinations, or the assessment of gene methylation. However, none of these tests is widely used in clinical practice. Nevertheless, starting from the initial patient assessment, prostate cancer risk groups and disease progression are difficult to predict reliably, and challenges remain in finding a combination of biomarkers and clinical data that can be used for this purpose.

• Related topic: Is Gleason 6 Prostate Cancer and Should It Be Treated?

Microbiota and Cancer Development

Hereditary factors and ethnicity have a known role in the development of prostate cancer, and chronic inflammation has also been proposed as a causal factor.

Chronic infection caused by Helicobacter pylori bacteria is the most important cause of stomach cancer, encouraging research into microbial involvement in the development of other cancers as well.

Bacteria are known to exist in the urogenital tract and prostate tissue, and bacteria isolated from the prostate can cause inflammation in animal models.

Microbes in prostate tissue differ among patients with different Gleason scores, and there are links between the presence of prostate cancer and different microbial profiles in urine and the gastrointestinal tract.

A review published in 2019 examined the relationship between the microbiome and prostate pathologies, but concluded that major challenges remain;

• Sample contamination
• Obtaining an effective control group of tissue
• Classifying newly involved bacteria, which frequently appear

Following this, in an article published in European Urology Oncology researchers improved upon the above conditions and examined the relationship between the presence of bacteria and prostate cancer risk groups.

The study used urine samples collected before biopsy from patients undergoing biopsy for prostate cancer or hematuria (blood in the urine) at Norfolk and Norwich University Hospitals in England, and prostate secretions obtained from prostates after prostatectomy.

• First, a significant linear relationship was demonstrated between high-risk prostate cancer groups and the presence of certain bacteria (detection was performed by fluorescence microscopic analysis of bacterial DNA).
• Second, a subgroup of patients with a higher metastatic disease burden was identified. This observation led to the development of the ABBS (Anaerobic Bacteria Biomarker Set), consisting of five species of anaerobic bacteria (see Figure 1).
• Third, the analysis of urine samples provided indicative results supporting the importance of ABBS. Information about bacteria in prostatectomy tumor samples also confirmed the importance of ABBS in tissue.

Taken together, these studies provide strong information on the role of certain ABBSs in the prostate-urine reflux cycle in predicting aggressive prostate cancer.

Conclusion

All studies on this subject consistently reach the conclusion that microbiomes in cancer tissue or blood can be used as biomarkers to diagnose multiple cancer types and predict the course of disease.

The bacteria in the Anaerobic Bacteria Biomarker Set (ABBS) identified in this current study have also been shown to exist in other cancer types. This may therefore help move beyond the method used to determine whether prostate cancer is aggressive.

Further studies are needed to determine whether ABBS-specific bacteria cause cancer, identify any pathogenic processes, and subsequently identify potential treatment options that can eliminate anaerobic pathogens.

In conclusion, this newly published study has demonstrated the importance of bacteria in urine and the prostate as potential markers for predicting the course of disease. Considered alongside previous studies, this new study will be a starting point for future research focusing on the roles of bacteria in the pathogenesis and evolution of prostate cancer.