1. An exploratory study investigating the impact of the bladder tumor microbiome on Bacillus Calmette Guerin (BCG) response in non-muscle invasive bladder cancer.
- Author
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Knorr J, Lone Z, Werneburg G, Adler A, Agudelo J, Suryavanshi M, Campbell RA, Ericson K, Qiu H, Bajic P, Haber GP, Weight CJ, Ahern PP, Almassi N, Miller AW, and Lee BH
- Subjects
- Humans, Male, Female, Aged, Retrospective Studies, Middle Aged, Neoplasm Invasiveness, Adjuvants, Immunologic therapeutic use, Treatment Outcome, Administration, Intravesical, Non-Muscle Invasive Bladder Neoplasms, Urinary Bladder Neoplasms microbiology, Urinary Bladder Neoplasms pathology, Urinary Bladder Neoplasms drug therapy, BCG Vaccine therapeutic use, Microbiota
- Abstract
Purpose: Intravesical Bacillus Calmette-Guerin (BCG) is standard of care for intermediate- and high-risk non-muscle invasive bladder cancer (NMIBC). The effect of the bladder microbiome on response to BCG is unclear. We sought to characterize the microbiome of bladder tumors in BCG-responders and non-responders and identify potential mechanisms that drive treatment response., Materials and Methods: Patients with archival pre-treatment biopsy samples (2012-2018) were identified retrospectively. Prospectively, urine and fresh tumor samples were collected from individuals with high-risk NMIBC (2020-2023). BCG response was defined as tumor-free 2 years from induction therapy. Extracted DNA was sequenced for 16S rRNA and shotgun metagenomics. Primary outcomes were species richness (α-diversity) and microbial composition (β-diversity). Paired t-tests were performed for α-diversity (Observed species/Margalef). Statistical analysis for β-diversity (weighted and unweighted UniFrac distances, weighted Bray-Curtis dissimilarity) were conducted through Permanova, with 999 permutations., Results: Microbial species richness (P < 0.001) and composition (P = 0.001) differed between BCG responders and non-responders. Lactobacillus spp. were significantly enriched in BCG-responders. Shotgun metagenomics identified possible mechanistic pathways such as assimilatory sulfate reduction., Conclusion: A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders., Competing Interests: Declaration of competing interest We declare that we have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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