Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.
Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients.
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DOI：
10.1038/s41467-020-18649-5
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发表时间：
2020-09-24
影响因子：
16.6
通讯作者：
Burton JP
中科院分区：
文献类型：
--
作者：
Daisley BA;Chanyi RM;Abdur-Rashid K;Al KF;Gibbons S;Chmiel JA;Wilcox H;Reid G;Anderson A;Dewar M;Nair SM;Chin J;Burton JP
醋酸阿比特龙（AA）是雄激素生物合成的抑制剂，尽管这不能完全解释其对雄激素非依赖性前列腺癌的疗效。在这里，我们证明，雄激素剥夺治疗消耗雄激素利用棒状杆菌属。在前列腺癌患者中，口服AA进一步富集了健康相关嗜粘蛋白阿克曼氏菌。功能推断阐明了维生素K2（雄激素依赖性和非依赖性肿瘤生长的抑制剂）的细菌生物合成的同时增加。这些结果在无宿主肠道模型中具有高度重现性，排除了免疫参与的可能性。进一步的研究表明，AA在体外被细菌代谢，并且分解组分选择性地影响生长。我们的结论是A.嗜粘蛋白菌是AA介导的微生物群落重组的关键调节因子，该种属可能影响去势抵抗性队列的治疗反应。正在进行的旨在调节癌症患者结肠微生物群的计划可能会考虑靶向递送吸收不良的选择性细菌生长剂。醋酸阿比特龙（AA）适用于治疗转移性去势抵抗性前列腺癌患者。在这里，作者表明，在前列腺癌患者中，口服AA重塑了肠道微生物组，并以利用雄激素的棒状杆菌物种为代价促进了嗜粘蛋白阿克曼氏菌的富集。
Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents. Abiraterone acetate (AA) is indicated for the treatment of patients with metastatic castrate-resistant prostate cancer. Here, the authors show that, in prostate cancer patients, orally administered AA remodels the gut microbiome and promotes the enrichment of the commensal bacterium Akkermansia muciniphila at the expense of androgen-utilizing Corynebacterium species.
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DOI：
10.1016/j.jsbmb.2003.09.005
发表时间：
2003-12-01
影响因子：
4.1
作者：
Decréau, RA;Marson, CM;Behan, JM
通讯作者：
Behan, JM
DOI：
10.1038/ismej.2012.8
发表时间：
2012-08
期刊：
The ISME journal
影响因子：
--
作者：
通讯作者：
--
影响因子：
15.5
作者：
Fenn K;Strandwitz P;Stewart EJ;Dimise E;Rubin S;Gurubacharya S;Clardy J;Lewis K
通讯作者：
Lewis K
影响因子：
4.3
作者：
Faust K;Sathirapongsasuti JF;Izard J;Segata N;Gevers D;Raes J;Huttenhower C
通讯作者：
Huttenhower C
影响因子：
23.4
作者：
Cavarretta, Ilaria;Ferrarese, Roberto;Salonia, Andrea
通讯作者：
Salonia, Andrea