Fujimoto Saizo, Hatano Koji, Banno Eri, Motooka Daisuke, De Velasco Marco Antonio, Kura Yurie, Toyoda Shingo, Hashimoto Mamoru, Adomi Shogo, Minami Takafumi, Yoshimura Kazuhiro, Oka Toshiki, Hata Junya, Matsushita Makoto, Takao Tetsuya, Takada Shingo, Tsujimura Akira, Kojima Yasuyuki, Obara Wataru, Nakamura Shota, Uemura Hirotsugu, Nonomura Norio, Fujita Kazutoshi
Department of Urology, Kindai University School of Medicine, Osaka-Sayama, Japan.
Department of Urology, Osaka University Graduate School of Medicine, Suita, Japan.
Cancer Sci. 2025 Feb;116(2):462-469. doi: 10.1111/cas.16408. Epub 2024 Dec 3.
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.
肠道微生物群在前列腺癌的发生和发展中起着至关重要的作用，先前的研究表明，与激素敏感性前列腺癌（HSPC）相比，某些细菌类群在去势抵抗性前列腺癌（CRPC）中更为丰富。值得注意的是，肠道微生物群的组成可能因地理区域而有显著差异，日本人具有独特的微生物特征。然而，探索日本人群中这些差异的研究仍然有限。本研究调查了患有HSPC和CRPC的日本男性之间肠道微生物群的差异，并使用转基因小鼠模型进一步验证了这些发现。在2020年9月至2022年7月期间，从140名被诊断为HSPC（n = 84）或CRPC（n = 56）的日本男性中收集直肠拭子样本。使用16S rRNA基因测序分析肠道微生物群组成。此外，对模拟从HSPC进展到CRPC的Pten-KO小鼠进行了类似的微生物群分析。结果显示，HSPC和CRPC患者的肠道微生物群组成存在显著差异。具体而言，与HSPC组相比，CRPC组中厚壁菌门（包括孪生球菌属和乳杆菌属）的丰度更高。这些差异在小鼠模型中也得到了体现，CRPC小鼠中这些细菌也有所增加。本研究确定了日本男性HSPC和CRPC之间不同的微生物差异，表明孪生球菌属和乳杆菌属可能与前列腺癌去势抵抗的进展有关。这些发现表明，肠道微生物群差异可能与前列腺癌进展有关。需要进一步研究以探索将微生物群作为治疗策略的潜力。
