Abstract

Simple SummaryThe link between bladder cancer and urinary microbiota has been of high interest, but few studies have shed the light on the concrete urinary species as the potential clinical biomarkers. In this article, we reported the previously ignored urinary speciesEubacteriumsp.CAG:581in predicting the occurrence of non-muscle invasive bladder cancer (NMIBC). Excluding the favorable impact of age, sex, smoking, alcohol consumption and other potential contributing factors, we have foundEubacteriumsp.CAG:581has contributed to the development of bladder cancer through activating the extracellular matrix protein 1-matrix metalloproteinase 9 pathway. In the cohort of 406 NMIBC patients and 398 healthy controls, we found that highEubacteriumsp.CAG:581will correctly distinguish an NMIBC patient from a healthy person by the chance of 79% within 3 years. Collectively, this study manifested thatEubacteriumsp.CAG:581may serve as the promising noninvasive diagnostic biomarker for NMIBC.AbstractBackground: Increasing evidence points to the urinary microbiota as a possible key susceptibility factor for early-stage bladder cancer (BCa) progression. However, the interpretation of its underlying mechanism is often insufficient, given that various environmental conditions have affected the composition of urinary microbiota. Herein, we sought to rule out confounding factors and clarify how urinaryEubacteriumsp.CAG:581promoted non-muscle invasive bladder cancer (NMIBC) development. Methods: Differentially abundant urinary microbiota of 51 NMIBC patients and 47 healthy controls (as Cohort 1) were first determined by metagenomics analysis. Then, we modeled the coculture of NMIBC organoids with candidate urinaryEubacteriumsp.CAG:581in anaerobic conditions and explored differentially expressed genes of these NMIBC tissues by RNA-Seq. Furthermore, we dissected the mechanisms involved intoEubacteriumsp.CAG:581by inducing extracellular matrix protein 1 (ECM1) and matrix metalloproteinase