研究人员发现，小鼠和人类的雄性激素剥夺促进了特定共生微生物群扩张，这有助于小鼠去势抵抗的发生。具体来说，小鼠和去势抵抗型前列腺癌（CRPC）患者的肠道微生物群落富含能够将雄性激素前体转化为活性雄性激素的物种。通过抗生素治疗消减肠道微生物群，甚至在免疫缺陷的小鼠中也能延迟去势抗性的出现。来自CRPC小鼠和患者的粪便微生物群移植（FMT）使患有前列腺癌小鼠对去势产生抵抗。相反，肿瘤的生长被来自激素敏感型前列腺癌患者的FMT和Prevotella stercorea给药所控制。这些结果显示，共生肠道微生物群通过提供雄性激素的替代来源促进了CRPC的内分泌抵抗。
据了解，微生物群包括与宿主密切接触的微生物，这对双方都有益处。肠道微生物群对CRPC的贡献还没有得到解决。
附：英文原文
Title: Commensal bacteria promote endocrine resistance in prostate cancer through androgen biosynthesis
Author: Nicolò Pernigoni, Elena Zagato, Arianna Calcinotto, Martina Troiani, Ricardo Pereira Mestre, Bianca Calì, Giuseppe Attanasio, Jacopo Troisi, Mirko Minini, Simone Mosole, Ajinkya Revandkar, Emiliano Pasquini, Angela Rita Elia, Daniela Bossi, Andrea Rinaldi, Pasquale Rescigno, Penny Flohr, Joanne Hunt, Antje Neeb, Lorenzo Buroni, Christina Guo, Jonathan Welti, Matteo Ferrari, Matteo Grioni, Josée Gauthier, Raad Z. Gharaibeh, Anna Palmisano, Gladys Martinetti Lucchini, Eugenia D’Antonio, Sara Merler, Marco Bolis, Fabio Grassi, Antonio Esposito, Matteo Bellone, Alberto Briganti, Maria Rescigno, Jean-Philippe Theurillat, Christian Jobin, Silke Gillessen, Johann de Bono, Andrea Alimonti
Issue&Volume: 2021-10-08
Abstract: 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.
DOI: abf8403
Source: https://www.science.org/doi/10.1126/science.abf8403