Cosma-Grigorov Alexandra, Meixner Holger, Mrochen Anne, Wirtz Stefan, Winkler Jürgen, Marxreiter Franz
Department of Molecular Neurology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), University Hospital Erlangen, Erlangen, Germany.
Department of Neurology and Neuroscience, Albert-Ludwigs-University Medical Center Freiburg, Freiburg, Germany.
Front Neurol. 2020 Sep 23;11:1041. doi: 10.3389/fneur.2020.01041. eCollection 2020.
Altered gut microbiota may trigger or accelerate alpha-synuclein aggregation in the enteric nervous system in Parkinson's disease (PD). While several previous studies observed gut microbiota alterations in PD, findings like diversity indices, and altered bacterial taxa itself show a considerable heterogeneity across studies. We recruited 179 participants, of whom 101 fulfilled stringent inclusion criteria. Subsequently, the composition of the gut microbiota in 71 PD patients and 30 healthy controls was analyzed, sequencing V3-V4 regions of the bacterial 16S ribosomal RNA gene in fecal samples. Our goal was (1) to evaluate whether gut microbiota are altered in a southern German PD cohort, (2) to delineate the influence of disease duration, stage, and motor impairment, and (3) to investigate the influence of PD associated covariates like constipation and coffee consumption. Aiming to control for a large variety of covariates, strict inclusion criteria were applied. Finally, propensity score matching was performed to correct for, and to delineate the effect of remaining covariates (non-motor symptom (NMS) burden, constipation, and coffee consumption) on microbiota composition. Prior to matching altered abundances of distinct bacterial classes, orders, families, and genera were observed. Both, disease duration, and stage influenced microbiome composition. Interestingly, levodopa equivalent dose influenced the correlation of taxa with disease duration, while motor impairment did not. Applying different statistical tests, and after propensity score matching to control for NMS burden, constipation and coffee consumption, and were most consistently reduced in PD compared to controls. Taken together, similar to previous studies, alterations of several taxa were observed in PD. Yet, further controlling for PD associated covariates such as constipation and coffee consumption revealed a pivotal role of these covariates. Our data highlight the impact of these PD associated covariates on microbiota composition in PD. This suggests that altered microbiota may mediate the protective effect of i.e., coffee consumption and the negative effect of constipation in PD.
肠道微生物群的改变可能会触发或加速帕金森病（PD）患者肠神经系统中α-突触核蛋白的聚集。虽然之前的几项研究观察到了PD患者的肠道微生物群改变，但多样性指数等结果以及细菌分类群本身的改变在不同研究中显示出相当大的异质性。我们招募了179名参与者，其中101名符合严格的纳入标准。随后，分析了71名PD患者和30名健康对照者的肠道微生物群组成，对粪便样本中细菌16S核糖体RNA基因的V3-V4区域进行测序。我们的目标是：（1）评估德国南部PD队列中的肠道微生物群是否发生改变；（2）描述疾病持续时间、阶段和运动障碍的影响；（3）研究便秘和咖啡消费等与PD相关的协变量的影响。为了控制各种协变量，应用了严格的纳入标准。最后，进行倾向评分匹配以校正并描述剩余协变量（非运动症状（NMS）负担、便秘和咖啡消费）对微生物群组成的影响。在匹配之前，观察到不同细菌类、目、科和属的丰度改变。疾病持续时间和阶段均影响微生物组组成。有趣的是，左旋多巴等效剂量影响分类群与疾病持续时间的相关性，而运动障碍则没有。应用不同的统计测试，并在进行倾向评分匹配以控制NMS负担、便秘和咖啡消费后，与对照组相比，PD患者中 和 最一致地减少。综上所述，与之前的研究相似，在PD中观察到了几个分类群的改变。然而，进一步控制与PD相关的协变量，如便秘和咖啡消费，揭示了这些协变量的关键作用。我们的数据突出了这些与PD相关的协变量对PD患者微生物群组成的影响。这表明，改变的微生物群可能介导了例如咖啡消费的保护作用以及便秘在PD中的负面影响。
