Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 5:13:1125809.
doi: 10.3389/fcimb.2023.1125809. eCollection 2023.

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer

Christopher James  1 , Kayeromi Gomez  2 , Shalin Desai  1 , Hiten D Patel  1   3 , Goran Rac  1 , Chirag P Doshi  1 , Ryan Dornbier  1 , Petar Bajic  1   4   5 , Thomas Halverson  5 , Gopal N Gupta  1 , Marcus L Quek  1 , Alex Gorbonos  1 , Robert Flanigan  1 , Alan J Wolfe  4   5
Affiliations

Impact of intravesical Bacillus Calmette-Guérin and chemotherapy on the bladder microbiome in patients with non-muscle invasive bladder cancer

Christopher James et al. Front Cell Infect Microbiol. .

Abstract

Introduction: Intravesical therapy (IVT), including Bacillus Calmette-Guérin (BCG), is the standard of care for high grade (HG) non-muscle invasive bladder cancer (NMIBC). Despite the use of IVT, many patients recur after treatment. The bladder microbiome and its role in disease processes has recently risen to prominence. We aim to characterize changes that occur in the bladder microbiome over the course of intravesical therapy and assess whether these changes correlate with outcomes in patients with NMIBC.

Methods: Patients with NMIBC undergoing induction BCG or intravesical therapy were prospectively enrolled from January 2019 to March 2020. Patients with clinical T2 or greater pathology or active urinary tract infection at enrollment were excluded. Twenty-nine patients had catheterized (bladder) urine samples collected prior to induction intravesical therapy and prior to each IVT instillation. Twenty-seven received BCG while 2 received intravesical gemcitabine. Bacteria were identified using 16S ribosomal RNA gene sequencing. Bladder microbiome changes were evaluated and differences between patients who recurred and patients who did not recur after IVT were investigated.

Results: Across the 29 patients analyzed, bacterial richness decreased significantly following intravesical therapy (Richness, P=0.01). Evenness and overall diversity did not change significantly (Pielou, P=0.62; Shannon, P=0.13). Patients who experienced recurrence had a higher relative abundance of Aerococcus in their urine (P<0.01), while those who did not recur had significantly more Ureaplasma (P=0.01) and Escherichia/Shigella species (P=0.05). Patients with decreased levels of alpha diversity were more likely to fall within the non-recurrence cohort.

Conclusion: IVT for NMIBC appears to change the urinary microbiome by decreasing richness while not altering evenness or overall diversity. The presence of Aerococcus species may be predictive of a poor cancer response to IVT, while the presence of Ureaplasma and Escherichia/Shigella may predict a favorable response to IVT. Further studies are warranted to elucidate and confirm the significance of changes in the bladder microbiome.

Keywords: Bacillus Calmette-Guérin (BCG); bladder cancer; intravesical gemcitabine; intravesical therapy; microbiome.

PubMed Disclaimer

Conflict of interest statement

AW - Membership on the Urobiome Therapeutics advisory board, membership on the Pathnostics Scientific Advisory Board, research funding from the NIH, the Craig H. Neilsen Foundation, and Pathnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Box plot demonstrating Shannon Diversity Index measures for non-recurrence and recurrence patients within the cohort across beginning, middle and end timepoints. The y-axis displays the value of the Shannon Diversity Index. The x-axis indicates timepoint.
See this image and copyright information in PMC

References

    1. Alexander J. L., Wilson I. D., Teare J., Marchesi J. R., Nicholson J. K., Kinross J. M. (2017). Gut microbiota modulation of chemotherapy efficacy and toxicity. Nat. Rev. Gastroenterol. Hepatol. 14 (6), 356–365. doi: 10.1038/nrgastro.2017.20 - DOI - PubMed
    1. American Cancer Society . (2022). Intravesical therapy for bladder cancer. Am. Cancer Soc. - Intravesical Ther. Bladder Cancer.
    1. Bucevic Popovic V., Situm M., Chow C. T., Chan L. S., Roje B., Terzic J. (2018). The urinary microbiome associated with bladder cancer. Sci. Rep. 8 (1), 12157. doi: 10.1038/s41598-018-29054-w - DOI - PMC - PubMed
    1. Callahan B. J., McMurdie P. J., Rosen M. J., Han A. W., Johnson A. J., Holmes S. P. (2016). DADA2: High-resolution sample inference from illumina amplicon data. Nat. Methods 13 (7), 581–583. doi: 10.1038/nmeth.3869 - DOI - PMC - PubMed
    1. Davis N. M., Proctor D. M., Holmes S. P., Relman D. A., Callahan B. J. (2018). Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data. Microbiome 6 (1), 226. doi: 10.1186/s40168-018-0605-2 - DOI - PMC - PubMed

Publication types

MeSH terms