Cell:肠道菌会改变抗癌药物的活性

2017-04-26 佚名 生物探索

美国UCL大学领导的研究分析了线虫中药物和营养的微生物过程,该研究显示癌症药物的活性变化取决于生活在肠道内的细菌种类。这一发现凸显了操纵肠道菌和饮食来改善癌症治疗的潜在益处,以及了解个体间药物效用差异的价值。这篇研究文章发表在4月21的 cell上,通过一个新的高通量筛选方法,阐明了宿主之间复杂的关系,以及肠道微生物与药物的作用。研究人员回应媒体采访研究的领导者Filipe Cabreiro博士说

美国UCL大学领导的研究分析了线虫中药物和营养的微生物过程,该研究显示癌症药物的活性变化取决于生活在肠道内的细菌种类。这一发现凸显了操纵肠道菌和饮食来改善癌症治疗的潜在益处,以及了解个体间药物效用差异的价值。

这篇研究文章发表在4月21的 cell上,通过一个新的高通量筛选方法,阐明了宿主之间复杂的关系,以及肠道微生物与药物的作用。

研究人员回应媒体采访

研究的领导者Filipe Cabreiro博士说:“大肠癌患者的治疗效果差别很大。我们想知道这是否可能是由微生物改变身体如何处理药物引起的。我们已经开发出了严格的体系,可用于在宿主和微生物中药物相互作用的临床前筛选,或为药物递送设计细菌进行革命性的治疗。”

文章的第一作者Timothy Scott博士说:“我们忘记了我们体内存在着许多与食物和药物相互作用的有机体。到目前为止,探索宿主、微生物和药物之间的关系被证明是困难的。通常分离微生物的方法是不现实的,但运用我们现在开发的体内的方法,对于药物活性如何获得肠道微生物的支持或抑制,我们已经有了一些惊人的见解。”

线虫是个理想的模式生物

研究小组开发了一种基于线虫的筛选方法。线虫通常在研究人类新陈代谢中被作为一个简单的模型,因为它在进化上比人类简单但其和微生物的关系和人类却又有可比性。

他们通过改变细菌基因以及药物种类和剂量,在线虫中筛选了55000个不同的条件。然后利用计算机分析详尽地分析了细菌的遗传、饮食来源和化学物质对氟尿嘧啶影响的效果。氟尿嘧啶是大肠癌药物的一个常见类型。

氟尿嘧啶类药物通过阻止DNA的产生而作用,防止细胞以不受控制的方式分裂,这是癌细胞的典型特征。它们通常以前体药物的形式存在,这意味着需要肝脏将其分解成活性药物。尽管氟尿嘧啶是一种常见的癌症治疗药物,但目前没有普遍接受的剂量标准,光用遗传学无法给出病人对药物反应差异的解释。

有些肠道菌增强大肠癌药物的活性

在这项研究中的广泛筛选用了三种不同的方法,证实细菌改变线虫中的药物活性。首先,一些细菌有助于将前体药物转化为活性药物形式,增强药物的活性;其次,细菌影响细胞的代谢环境,使其更容易发生药物引导的细胞死亡。

研究小组还发现,如果不考虑宿主-微生物-药物相互作用,癌症的联合治疗的成功可能是有限的。例如,他们发现抗糖尿病药物二甲双胍通过抑制细菌的积极行动,会减少氟尿嘧啶在线虫中的效果。

Cabreiro博士得出的结论是:“我们在药物是如何治疗疾病方面,补上了一个关键的缺失成分——肠道菌。我们计划在该领域深入研究,识别哪些微生物是负责在人体中的药物活性起作用,并通过膳食补充剂的监管能对癌症的治疗结果产生巨大影响。”

原始出处:

Scott TA, Quintaneiro LM, Norvaisas P,et al.Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans.Cell. 2017 Apr 20

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    2018-04-04 维他命
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    2017-05-28 lofter

    学习了,感谢分享

    0

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    2017-04-28 sunylz
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    2017-04-26 flysky120

    学习新知识了,新内容

    0

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    2017-04-26 医艺依意

    学习了,谢谢分享

    0

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