SUO 2018: Bladder Cancer and the Microbiome: Emerging Evidence
According to Dr. Steinberg, urine is not sterile, and sequencing with 16s ribosomal RNA amplification demonstrates that the urine is replete with various microorganism that are not usually grown in standard urine cultures (1). There are many potential roles of the urine microbiota, including commensal or pathogen. Furthermore, in the urine, bacteria produce neurotransmitters to interact and they may regulate the maintenance of epithelial junctions. Commensal bacteria may produce antimicrobials to kill pathogens and degrade harmful products. They may also prime epithelial and immune defenses.
Signaling molecules and metabolic products of the microbiota influence many intestinal functions: visceral-sensing, motility, digestion, permeability secretion, energy harvest, mucosal immunity, and barrier effect. Furthermore, the components of the microbiota could potentially enter the circulation and be transported to various organs affecting their functionality. Bacterial structural components and their metabolites are significant forces that can induce the development and maturations of organs, and physiological processes in the host. This demonstrates the importance of the microbial ecosystem in maintaining a healthy status. This intestinal microbial ecosystem balance, called eubiosis, is a fundamental concept. In contrast, when balance does not exist anymore, and bacteria do not live together in mutual harmony within our body, a condition called dysbiosis occurs, potentially leading to the development of cancer.
In a study from China, midstream urine was collected from 31 bladder cancer patients and compared to 18 controls (2). Sequencing was performed using 16s ribosomal RNA. The hypothesis was that bladder cancer patients will be enriched with different bacteria than controls. The results demonstrated difference in bacterial diversity among bladder cancer risk but not grade. Specific bacteria were more common among bladder cancer patients and other bacteria were more common among controls. The bacteria more common in bladder cancer patients include Acinetobacter, aneurococcus, and sphingobacterium.
A prospective double blind randomized controlled study assessed the role of probiotics and bladder cancer. This study compared prophylactic lactobacillus to placebo. A total of 138 patients with high and low grade non-muscle invasive bladder cancer were randomized. The results demonstrated that lactobacillus was associated with reduction in recurrence (p=0.01).
Another nested case control study assessing 15 malignancies in a large population EMR database demonstrated that bladder cancer risk was significantly increased with specific antibiotics (3). The authors concluded that recurrent exposure to antibiotics may be associated with increased cancer risk. Work presented from the University of Chicago suggested that patients with recurrent bladder cancer have difference in the type of bacteria in their urine.
In conclusion, the complex understanding of the microbiome and the interaction with bladder cancer continues to evolve, and to date, little is known about the urinary microbiome in these patients. Bacteria may play a critical role in carcinogenesis, and response immunotherapy, and further clinical trials are needed to fully understand the role of microbiota in these patients.
Presented By: Gary D. Steinberg, University of Chicago, Chicago, IL, USA
References:
Whiteside et al. Nature 2015
Wu P et al. Front Cell Infect Microbiol. 2018
Boursi B et al. Eur J Cancer 2015
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow, SUO, University of Toronto, Princess Margaret Cancer Centre, @GoldbergHanan, at the 19th Annual Meeting of the Society of Urologic Oncology (SUO), November 28-30, 2018 – Phoenix, Arizona