School of Medicine and Health Sciences Poster Presentations

Title

Profiling of Urine Bacterial DNA to Identify an “Oncobiome” in a Mouse Model of Bladder Cancer

Poster Number

127

Document Type

Poster

Status

Scientist

Abstract Category

Cancer/Oncology

Keywords

bladder cancer, oncobiome, microbiome, mouse model

Publication Date

Spring 2018

Abstract

Although the bladder has traditionally been thought to be sterile, recent research has demonstrated that a variety of organisms colonize the bladder in health and disease states. The urine microbiome likely influences the onset and progression of bladder cancer, but precisely how is not known. Work by others has conversely shown that while chronic cystitis may be a risk factor for bladder cancer, bladder cancer patients with asymptomatic bacteriuria have a lower rate of tumor recurrence. We hypothesize that certain urine microbiome profiles may be linked to bladder cancer (the “oncobiome”). Our objective is to identify this oncobiome in a mouse model of bladder cancer. In a pilot study, a mouse given a dilute nitrosamine via the drinking water (0.1% n-butyl-n-(4-hydroxybutyl) nitrosamine, BBN), a bladder-specific carcinogen, had an altered bacterial community structure as compared to control mice. We then conducted a longitudinal study in which urine was collected from BBN-exposed and control mice over 5 months (n = 10, each group). At study conclusion, bladders were harvested and subjected to blinded pathological analysis. Bacterial DNA was isolated from the urine and oncobiome analysis was conducted by bacterial 16S rRNA V4 amplicon sequencing. A range of bladder pathologies were observed, including dysplasia, carcinoma in situ, and invasive cancer. Urine oncobiome analysis showed no differences between BBN and control groups at baseline, but greater diversity and relative abundances/deficiencies of certain species in the BBN mice as early as 1 month after beginning the study, although the profiles of both control and BBN-treated mice varied over time. While no bacterial group was consistently over- or under-represented in the BBN mice for the duration of the experiment, the Pasteurellaceae were over-abundant in multiple time points. Additional analyses and confirmatory experiments are currently underway. We will also test our central hypothesis in additional mouse models and by profiling human samples. Finally, we speculate that it may be possible to prevent or treat bladder cancer by manipulation of the bladder oncobiome.

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Profiling of Urine Bacterial DNA to Identify an “Oncobiome” in a Mouse Model of Bladder Cancer

Although the bladder has traditionally been thought to be sterile, recent research has demonstrated that a variety of organisms colonize the bladder in health and disease states. The urine microbiome likely influences the onset and progression of bladder cancer, but precisely how is not known. Work by others has conversely shown that while chronic cystitis may be a risk factor for bladder cancer, bladder cancer patients with asymptomatic bacteriuria have a lower rate of tumor recurrence. We hypothesize that certain urine microbiome profiles may be linked to bladder cancer (the “oncobiome”). Our objective is to identify this oncobiome in a mouse model of bladder cancer. In a pilot study, a mouse given a dilute nitrosamine via the drinking water (0.1% n-butyl-n-(4-hydroxybutyl) nitrosamine, BBN), a bladder-specific carcinogen, had an altered bacterial community structure as compared to control mice. We then conducted a longitudinal study in which urine was collected from BBN-exposed and control mice over 5 months (n = 10, each group). At study conclusion, bladders were harvested and subjected to blinded pathological analysis. Bacterial DNA was isolated from the urine and oncobiome analysis was conducted by bacterial 16S rRNA V4 amplicon sequencing. A range of bladder pathologies were observed, including dysplasia, carcinoma in situ, and invasive cancer. Urine oncobiome analysis showed no differences between BBN and control groups at baseline, but greater diversity and relative abundances/deficiencies of certain species in the BBN mice as early as 1 month after beginning the study, although the profiles of both control and BBN-treated mice varied over time. While no bacterial group was consistently over- or under-represented in the BBN mice for the duration of the experiment, the Pasteurellaceae were over-abundant in multiple time points. Additional analyses and confirmatory experiments are currently underway. We will also test our central hypothesis in additional mouse models and by profiling human samples. Finally, we speculate that it may be possible to prevent or treat bladder cancer by manipulation of the bladder oncobiome.