Neoadjuvant chemotherapy (NAC) is linked with clinical advantages in urothelial carcinoma for patients with muscle-invasive bladder cancer (MIBC). Despite comprehensive research into the influence of tumor mutation expression profiles and clinicopathological factors on chemotherapy response, the role of the gut microbiome (GM) in bladder cancer(BC) chemotherapy response remains poorly understood. This study examines the variance in the gut microbiome(GM) of BC patients compared to healthy adults, and investigates GM compositional differences between patients who respond to chemotherapy versus those who exhibit residual disease. Our study reveals distinct clustering, effectively separating the BC and healthy cohorts. However, no significant differences were observed between chemotherapy responders and non-responders within community subgroups. Machine Learning models based on responder status outperformed clinical variables in predicting complete response (AUC 0.88 vs AUC 0.50), although no single microbial species emerged as a fully reliable biomarker. The evaluation of short-chain fatty acid (SCFA) concentration in blood and stool revealed no correlation with responder status. Still, SCFA analysis showed a higher abundance of Akkermansia (rs = 0.51, p = 0.017) and Clostridia (rs = 0.52, p = 0.018), which correlated with increased levels of detectable fecal isobutyric acid. Higher levels of fecal Lactobacillus (rs = 0.49, p=0.02) and Enterobacteriaceae (rs = 0.52, p < 0.03) correlated with increased fecal propionic acid. In conclusion, our study constitutes the first large-scale, multi-center assessment of GM composition, suggesting the potential for a complex microbial signature to predict patients more likely to respond to NAC based on multiple taxa.
Cancer research communications. 2024 May 15 [Epub ahead of print]
Laura Bukavina, Rashida Ginwala, Mohamed Eltoukhi, Mohit Sindhani, Megan Prunty, Daniel M Geynisman, Pooja Ghatalia, Henkel Valentine, Adam Calaway, Andres F Correa, Jason R Brown, Kirtishri Mishra, Elizabeth R Plimack, Alexander Kutikov, Mahmoud Ghannoum, Mohammed Elshaer, Mauricio Retuerto, Lee Ponsky, Robert G Uzzo, Philip H Abbosh
Fox Chase Cancer Center, Philadelphia, United States., Case Western Reserve University, United States., Indian Institute of Technology Delhi, India., University Hospitals Cleveland Medical Center, United States., Fox Chase Cancer Center, Philadelphia, PA, United States., Fox Chase Cancer Center, Birmingham, AL, United States., University Hospitals Case Medical Center, Cleveland, United States., University of Michigan-Ann Arbor, Ann Arbor, MI, United States., University Hospitals of Cleveland, United States., United States., Mansoura University, Mansoura, Egypt., University Hospitals Case Medical Center, Cleveland, Ohio, United States.