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.
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.
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.
A compositional difference exists in the tumor microbiome of BCG responders and non-responders with Lactobacillus having increased abundance in BCG responders.
Urologic oncology. 2024 Apr 24 [Epub ahead of print]
Jacob Knorr, Zaeem Lone, Glenn Werneburg, Ava Adler, Jose Agudelo, Mangesh Suryavanshi, Rebecca A Campbell, Kyle Ericson, Hong Qiu, Petar Bajic, Georges-Pascal Haber, Christopher J Weight, Philip P Ahern, Nima Almassi, Aaron W Miller, Byron H Lee
Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH., Cleveland Clinic Lerner College of Medicine, Cleveland, OH., Cleveland Clinic Lerner Research Institute, Cleveland, OH., Univeristy Hospitals Department of Urology, Cleveland, OH., Cleveland Clinic Glickman Urological and Kidney Institute, Cleveland, OH; Cleveland Clinic Lerner Research Institute, Cleveland, OH. Electronic address: ., University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: .