The microbiota comprises the microorganisms that live in close contact with the host, with mutual benefit for both counterparts. The contribution of the gut microbiota to the emergence of castration-resistant prostate cancer (CRPC) has not yet been addressed. We found that androgen deprivation in mice and humans promotes the expansion of defined commensal microbiota that contributes to the onset of castration resistance in mice. Specifically, the intestinal microbial community in mice and patients with CRPC was enriched for species capable of converting androgen precursors into active androgens. Ablation of the gut microbiota by antibiotic therapy delayed the emergence of castration resistance even in immunodeficient mice. Fecal microbiota transplantation (FMT) from CRPC mice and patients rendered mice harboring prostate cancer resistant to castration. In contrast, tumor growth was controlled by FMT from hormone-sensitive prostate cancer patients and Prevotella stercorea administration. These results reveal that the commensal gut microbiota contributes to endocrine resistance in CRPC by providing an alternative source of androgens.

中文翻译：

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共生菌通过雄激素生物合成促进前列腺癌的内分泌抵抗

微生物群包括与宿主密切接触的微生物，双方互惠互利。肠道微生物群对去势抵抗性前列腺癌 (CRPC) 出现的贡献尚未得到解决。我们发现小鼠和人类的雄激素剥夺促进了确定的共生微生物群的扩张，这有助于小鼠去势抵抗的发生。具体而言，小鼠和 CRPC 患者的肠道微生物群落富含能够将雄激素前体转化为活性雄激素的物种。即使在免疫缺陷小鼠中，通过抗生素疗法消融肠道菌群也可以延缓去势抵抗的出现。来自 CRPC 小鼠和患者的粪便微生物群移植 (FMT) 使患有前列腺癌的小鼠对去势具有抗性。相比之下，来自激素敏感的前列腺癌患者的 FMT 控制了肿瘤的生长和Prevotella stercorea管理。这些结果表明，共生肠道微生物群通过提供雄激素的替代来源而有助于 CRPC 的内分泌抵抗。