Nature:令人意外!一种常见的脑血管疾病竟与肠道微生物组存在关联

2017-05-11 生物谷 生物谷

根据一项新的研究,来自美国宾夕法尼亚大学佩雷尔曼医学院的研究人员报道,肠道微生物组中的细菌促进颅内海绵状血管瘤(cerebral cavernous malformation, CCM)形成。这项研究提示着改变CCM病人的肠道微生物组可能是一种有效地治疗这种脑血管疾病的方法。相关研究结果于2017年5月10日在线发表在Nature期刊上,论文标


根据一项新的研究,来自美国宾夕法尼亚大学佩雷尔曼医学院的研究人员报道,肠道微生物组中的细菌促进颅内海绵状血管瘤(cerebral cavernous malformation, CCM)形成。这项研究提示着改变CCM病人的肠道微生物组可能是一种有效地治疗这种脑血管疾病的方法。相关研究结果于2017年5月10日在线发表在Nature期刊上,论文标题为“Endothelial TLR4 and the microbiome drive cerebral cavernous malformations”。论文通信作者为宾夕法尼亚大学心血管医学教授Mark Kahn博士。

在CCM中,大脑内的扩张性薄壁血管簇集在一起,能够导致中风和癫痫。在每100~200人当中,大约有1人患上CCM。这种疾病存在两种形式。一种形式是散发性CCM,占所有CCM病例的80%。剩下 的20%是家族性的遗传性CCM病例。

在2016年,Kahn实验室已发现血管内皮细胞中促进CCM形成的分子通路(Nature, 07 April 2016, doi:10.1038/nature17178)。在当前的这项研究中,Kahn团队发现这个分子通路是由TLR4激活的。TLR4是细菌分子脂多糖(LPS)的一种受体。LPS激活大脑血管内皮细胞表面上的TLR4会极大地加快CCM形成。相反地,如果通过基因手段将TLR4从血管内皮细胞中移除,或者如果小鼠接受阻断TLR4功能的药物的处理,那么就可阻止CCM形成。

鉴于TLR4主要对来自革兰氏阴性菌的LPS作出反应,论文共同作者、Kahn实验室博士生Alan Tang提出来自小鼠肠道微生物组的细菌可能促进CCM形成。为了验证这个理论,他研究了在无菌环境下培养的或者通过抗生素处理降低生活在肠道中的细菌数量的小鼠体内的CCM形成。在这两种情形下,CCM形成显著下降,这就证实细菌在CCM病变过程中发挥着关键性作用。

Kahn团队接下来寻找证据来证实细菌LPS-TLR4信号可能也促进病人体内的CCM形成。他们与来自美国新墨西哥大学和加州大学旧金山分校的研究人员合作开展研究。他们研究了上百名CCM病人,这些病人在一个CCM基因中携带着一种相同的突变但表现出非常不同的病理过程。

Kahn说,“一些病人到2岁时经历严重的中风,其他的病人在一生当中都不会表现出症状。是什么让他们的病理过程存在如此大的不同?”

这些研究人员发现提高TLR4表达水平的基因变异与更高数量的CCM病灶存在关联,这提示着在小鼠体内鉴定出的LPS-TLR4信号发挥出的关键作用也存在于人体中。

这些研究结果鉴定出肠道微生物组与一种常见的脑血管疾病存在着一种出人意料之外的直接关联性。Kahn说,“这提示着旨在阻断TLR4信号或改变肠道微生物组的疗法可能被用来治疗这种疾病。”

原始出处:

Alan T. Tang, Jaesung P. Choi, Jonathan J. Kotzin et al. Endothelial TLR4 and the microbiome drive cerebral cavernous malformations. Nature, Published online 10 May 2017, doi:10.1038/nature22075

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    2017-11-23 liye789132251
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    2017-05-25 I come

    好文章,值得拜读

    0

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    2017-05-19 ylzr123

    好文,值得点赞!认真学习了,把经验应用于实践,为患者解除病痛。

    0

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