npj Parkinson's Disease:帕金森源于肠道又添新证,帕金森病患者肠道中有过量的机会性病原体

2020-06-23 Lauren 转化医学网

导言:在帕金森病(PD)中,胃肠道特征是很常见的,并且常常先于运动体征。早在2003年,德国科学家海科·布拉克(Heiko Braak)博士及其同事就提出,帕金森病可能开始于肠道,由病原

导言:在帕金森病(PD)中,胃肠道特征是很常见的,并且常常先于运动体征。早在2003年,德国科学家海科·布拉克(Heiko Braak)博士及其同事就提出,帕金森病可能开始于肠道,由病原体触发,然后传播到大脑。最近,阿拉巴马大学伯明翰分校的研究人员关于帕金森病与肠道的关系研究有了新的发现。

帕金森病(PD)是一种常见的、进行性的、使人衰弱的神经退行性疾病,目前还无法预防或治愈。

在2003年,海科·布拉克(Heiko Braak)就提出,非遗传性帕金森病是由肠道中的病原体引起的。他假设病原体能够穿过肠黏膜屏障,通过神经系统扩散到大脑。然而,直到目前为止,还没有证据表明一种特定的病原体可能触发帕金森病。

最近,来自阿拉巴马大学伯明翰分校(University of Alabama at Birmingham)的神经学教授海德·帕亚米(Haydeh Payami)博士和她的同事首次报道了,与对照组相比,帕金森病人的肠道中有大量的机会致病菌。该研究在6月12日发表在《自然》杂志上,题为“Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens”.

帕亚米表示,“令人兴奋的问题是,布拉克所讲的病原体是否能够触发帕金森病,或者这些病原体与帕金森无关,但能够穿透肠道进行生长,因为在帕金森病人中,肠道内膜有受损。我们强调,不能仅仅基于联想就声称有这种功能,这些微生物的身份将使实验研究能够确认它们是否以及如何在帕金森病人中发挥作用。”

帕亚米和来自阿拉巴马大学伯明翰分校、艾莫利大学、奥尔巴尼医学院和华盛顿大学的同事们可以鉴别出这些微生物,因为他们对帕金森病患者和对照组进行了迄今为止规模最大的全微生物关联研究(GWAS)。许多早期的研究已经发现,帕金森病人的肠道微生物改变了,但没有发现机会致病菌的增加。机会病原菌通常无害的,但如果免疫系统受损或侵入人体无菌部位,它们就会生长并引起感染

帕亚米表示,“我们怀疑我们能够检测到微生物的原因是它们非常罕见,而且我们的样本量和能量都比以前的研究大得多。”帕亚米和她的同事利用更先进的生物信息学渠道,重新分析了她们2017年的研究,该研究有197个病例和130个对照,使用了一个更先进的生物信息学通道。同时,她们还分析了一个新的独立数据集,其中有323个病例和184个对照。这允许内部复制,并检测罕见的和常见的信号的能力。早期帕金森微生物组的研究范围为10到197例帕金森病例和10到130例对照。


这两个数据集的肠道微生物组组成有显著差异。

早前,一项全微生物群关联研究使用先进的DNA测序和计算工具来寻找可能与疾病相关的微生物群落。人们逐渐认识到,肠道微生物包含500到1000种主要对人体有益的细菌,在人类健康和疾病中起重要作用。

在该研究中,研究人员还使用无假设相关网络分析来识别共生的微生物群落。网络分析是生物学中的一种重要的新工具。通过使用网络分析,帕亚米和她的同事们发现了了三个多微生物集群,每一个集群都具有相同的功能特征。

第一个集群就是由机会致病菌组成,在帕金森病患者中水平升高,这是一个新的发现。

另两个集群(一个是短链脂肪酸(SCFA)产生菌,另一个是碳水化合物代谢益生菌)在早期的研究中已经被证实。与对照组相比,帕金森病患者体内产生短链脂肪酸的微生物群水平较低,碳水化合物代谢益生菌水平升高。

关联网络分析将PD相关属映射为三种多菌群。

总之,该项研究证实了帕金森病患者中肠道微生物组的改变,并表明帕金森病对肠道微生物组整体组成的影响不受性别、年龄、体重指数、便秘、胃肠不适、地理位置和饮食的影响。研究人员通过使用假设无微生物相关性研究,确定了15个帕金森病相关的菌属。

原始出处:

Zachary D. Wallen, Mary Appah, Marissa N. Dean, et.al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens. npj Parkinson's Disease volume 6, Article number: 11 (2020)

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    2023-11-14 ms6000000799364627 来自山西省

    那究竟哪一个是致病菌呢?

    0

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    2020-08-28 杨小猫猫猫

    0

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    2020-06-25 xue8605
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