Comparative analysis of gut microbiota in hormone‐sensitive and castration‐resistant prostate cancer in Japanese men

Gut microbiota plays a crucial role in the development and progression of prostate cancer, with previous studies indicating that certain bacterial taxa are more abundant in castration-resistant prostate cancer (CRPC) compared to hormone-sensitive prostate cancer (HSPC). Notably, the composition of gut microbiota can vary significantly by geographic region, and Japanese individuals have a distinct microbial profile. However, research exploring these differences within Japanese populations remains limited. This study investigated the gut microbiota differences between Japanese men with HSPC and CRPC and further validated these findings using a transgenic mouse model. Rectal swab samples were collected from 140 Japanese men diagnosed with HSPC (n = 84) or CRPC (n = 56) between September 2020 and July 2022. Gut microbiota composition was analyzed using 16S rRNA gene sequencing. Additionally, Pten-KO mice, which model the progression from HSPC to CRPC, underwent similar microbiota analysis. Results revealed significant differences in gut microbiota composition between HSPC and CRPC patients. Specifically, the CRPC group showed a higher abundance of Firmicutes, including Gemella and Lactobacillus, compared to the HSPC group. These differences were mirrored in the mouse model, where CRPC mice also showed an increase in these bacteria. This study identifies distinct microbial differences between HSPC and CRPC in Japanese men, suggesting that Gemella and Lactobacillus may be associated with the progression to castration resistance in prostate cancer. These findings suggest that gut microbiota differences may be associated with prostate cancer progression. Further research is needed to explore the potential of targeting the microbiota as a therapeutic strategy.