Gut Microbiota Are Related to Parkinson's Disease and Clinical Phenotype
Gut Microbiota Are Related to Parkinson's Disease and Clinical Phenotype
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DOI：
10.1002/mds.26069
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发表时间：
2015-03-01
影响因子：
8.6
通讯作者：
Auvinen, Petri
中科院分区：
文献类型：
--
作者：
Scheperjans, Filip;Aho, Velma;Auvinen, Petri
在帕金森病(PD)的病程中，肠神经系统(ENS)和副交感神经是受α-突触核蛋白病理影响最早和最常见的结构之一。因此，胃肠功能障碍，特别是便秘，是帕金森病的一种重要的非运动症状，通常早于运动症状的出现数年。最近的研究表明，肠道微生物区系通过包括ENS和迷走神经在内的多种途径与自主神经和中枢神经系统相互作用。帕金森病患者的肠道微生物群以前没有被研究过。我们通过对细菌16S核糖体RNA基因的V1-V3区域进行焦糖测序，比较了72名PD患者和72名对照组的粪便微生物群。考虑到潜在的混杂因素，使用广义线性模型分析了临床参数和微生物区系之间的关联。帕金森病患者粪便中普氏杆菌丰度较对照组平均降低77.6%。Prevoteaceae相对丰度在6.5%或以下时，对PD的敏感性为86.1%，特异性为38.9%。基于4个细菌家族的丰度和便秘严重程度的Logistic回归分类器诊断PD患者的敏感度为66.7%，特异度为90.3%。肠杆菌科细菌的相对数量与姿势不稳和步态困难的严重程度呈正相关。这些发现提示帕金森病患者肠道微生物组发生改变，并与运动表型有关。需要进一步的研究来阐明肠道微生物区系和PD之间的时间和因果关系，以及微生物组作为生物标记物的适宜性。(C)2014年国际帕金森病和运动障碍协会
In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1-V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker. (c) 2014 International Parkinson and Movement Disorder Society