Abstract 1278: Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment

Abstract

Abstract Introduction & Objectives: Recent insights reveal a urinary microbiome, challenging prior beliefs about urine's sterility. Using 16S rRNA gene sequencing, a pivotal tool in mapping this microbiome, our study delves into the interplay between bladder cancer (BCa), BCG therapy, and the urinary microbiome. We analyzed bacterial profiles in benign and malignant samples, considering various clinical parameters. Materials & Methods: A total of 88 patients participated in the study, comprising 30 individuals with benign diseases and 58 BCa patients. Urine samples were collected from patients with benign conditions and from BCa patients before and after BCG treatment. Malignant samples obtained before the completion of the intravesical BCG induction cycle were labeled 'Pre-BCG', while those collected after this cycle were termed 'Post-BCG'. Following collection, DNA was extracted and underwent 16S rRNA gene sequencing. The sequencing data was then utilized for bioinformatic analyses, which included metagenomic profiling and metabolic pathway inference. Results: Significant differences in bacterial compositions were observed between benign and malignant samples, with a metabolic signature suggesting toluene degradation pathway may mitigate bladder cancer development. In the post-BCG samples, we inferred elevations of 2-oxoglutarate, a BCG derivative, and L-methionine, which is associated with therapeutic benefits, compared to their pre-BCG counterparts. Furthermore, post-BCG samples showed microbial differences in responders and increased quinolone synthesis compared to non-responders. This is of significance due to quinolone's role in modulating DNA topoisomerase and mitochondrial functions, both pivotal in bladder cancer progression. Conclusions: Utilizing 16S rRNA gene sequencing, we drew comparisons between the urinary microbiomes of benign and malignant samples and suggested a potential pathway for bladder cancer occurrence. Following intravesical BCG treatment, certain microbial metabolic pathways seemed to offer therapeutic benefits to responders. Our study provides insights into the microbial influences on bladder cancer development and the varying responses to BCG treatment. Citation Format: Xuan-Mei Piao, Kyungchan Min, Young Joon Byun, Chuang-Ming Zheng, Seon-Kyu Kim, Seong-Hwan Park, Sungmin Moon, Kyeong Kim, Ho Won Kang, Won Tae Kim, Seok Joong Yun, Hansoo Park. Differential urinary microbiome and its metabolic footprint in bladder cancer patients following BCG treatment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1278.