NPJ Parkinsons Dis:帕金森氏病肠道微生物群变化与肠道炎症有关

2021-03-17 MedSci原创 MedSci原创

肠道微生物区系正在成为神经退行性疾病的重要调节因子,越来越多的证据表明肠道微生物与帕金森病(PD)的症状和病理生理学有关。帕金森病通常先于胃肠道症状和伴随疾病的肠道神经系统改变。几项研究已经分析了帕金

肠道微生物区系正在成为神经退行性疾病的重要调节因子,越来越多的证据表明肠道微生物与帕金森病(PD)的症状和病理生理学有关。帕金森病通常先于胃肠道症状和伴随疾病的肠道神经系统改变。几项研究已经分析了帕金森病患者的肠道微生物群,但对帕金森病特异性微生物区系的特征缺乏共识。Stefano Romano等进行了Meta分析,重新分析目前可用的10个16S微生物群数据集,以调查PD患者肠道微生物区系中是否存在跨队列的共同改变,研究成果发表在NPJ Parkinsons Dis杂志。

近年来,一些研究已经分析报告了与健康对照组相比,帕金森病患者的肠道微生物群有不同程度改变的。该研究验证帕金森病患者肠道微生物群的一致变化是否可以在不同的研究中被识别出来。重新分析了所有可公开获得的16S rRNA基因扩增数据集,这些数据集是通过比较PD患者和健康对照而获得的,以提供对PD相关肠道微生物群的全面而有力的描述。研究在方法学方法上是不同的,研究间变异性是驱动细菌群落结构的主要因素,正如先前在饮食和结直肠癌的背景下进行的基于微生物组的荟萃分析所观察到的那样。该研究分析表明,特定的方法学方法,如样本收集和运输,测序平台,以及16S rRNA基因选择的可变区,可能是研究者考虑的数据集之间异质性的主要原因。此外,生物信息学方法之间存在一些差异,使用16S rRNA基因的V3-V4区域和通过TSS或CLR标准化的数据获得了最稳健和可比较的结果。他们重新分析的所有研究的可变性也反映了抽样人群的差异,以及招募参与者所使用的标准。例如,抗生素的使用并不总是被作为排除标准,当纳入时,在最后一次治疗和样本采集之间选择不同的时间间隔(即1个月和3个月)。混杂因素和反向因果关系也可能解释观察到的关联。尤其是,绝大多数帕金森病患者使用与帕金森病相关的药物(如左旋多巴),大多数病例是病情进展的,在一些研究中,对照组在年龄、性别和种族方面与患者有很大不同。因此,需要强调的是,使用现有数据不可能确定报告的关联是否与帕金森病有因果关系。未来的研究应该集中于标准化招募标准,优先关注早期药物未成熟的患者,以评估微生物群改变与帕金森病之间的因果关系。

PD患者和对照组之间的丰度存在显着差异。

总之,该研究的分析显示PD 患者和对照组之间的平均肠道菌群组成的一致性差异。研究之间的变化是塑造数据结构的最强大的因素,不同研究和国家之间PD 中肠道微生物组的改变是一致的。补充数据集将有助于更好地量化 PD 和对照组之间观察到的差异,帮助确定该研究无法解决的国别影响。此外,在可用的元数据的异质性使该研究无法考虑更详细的混杂因素,如共病率、药物治疗、饮食。这些数据将有助于进一步完善 PD 和微生物组之间的关联,并确定可能与疾病有关的类群。

PD 和对照组之间的类群丰度的差异表明, PD 患者的肠道菌群与其他神经系统疾病(如多发性硬化)和炎症性胃肠疾病有相似之处。重要微生物类群通过产生SCFA 维持肠道完整性和健康,而PD患者SCFA耗尽,另外,越来越多的证据表明PD患者存在肠道和全身炎症,上述发现表明,肠道菌群在调节PD患者免疫功能方面起着重要作用。此外,该研究能够确定以前被忽视的类群富集在PD ,如 Metanobrevibacter 和 Butyricicocaceae,并发现了一些潜在的新的代谢途径,微生物群可能通过这些途径影响 PD。该研究的研究结果与越来越多的证据表明,PD存在肠道和全身炎症,肠道菌群失调可能会影响宿主的免疫功能,并与 PD 患者经常观察到的胃肠道症状有关。

该研究发现帕金森病相关的微生物群发生了显著的变化,这对研究特定的技术异质性具有很强的抵抗力,尽管帕金森病患者和对照组之间的微生物群结构差异很小。乳杆菌属(Lactobacillus)、阿克曼西亚属(Akkermansia)和双歧杆菌属(Bifidobacterium)富含乳杆菌属(Lachnospiraceae)和双歧杆菌属(Faecalibacterium)这两个重要的短链脂肪酸产生菌,它们的富集和枯竭是PD肠道微生物群变化最一致的原因。这种生物失调可能导致促炎状态,这可能与PD患者反复出现的胃肠道症状有关

原文出处:

Romano Stefano,Savva George M,Bedarf Janis R et al. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation.[J] .NPJ Parkinsons Dis, 2021, 7: 27.

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帕金森氏症的特征是存在异常的神经内α-突触核蛋白聚集体,它可能以一种类似朊病毒的方式在细胞间传播。最令人感到困惑的是,帕金森氏症患者的症状之间有非常大的差异。

Annals of Neurology:帕金森病患者,深部脑刺激术后运动表现的预测因素

帕金森病患者,深部脑刺激术后运动表现的预测因素

Annals of Neurology: 伴有体位性低血压的帕金森病痴呆患者,卡巴拉汀可改善其认知功能

伴有体位性低血压的帕金森病痴呆患者,卡巴拉汀可改善其认知功能