Background:Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson’s disease (PD), prospective studies on de novo patients are lacking. Objective:To preliminarily investigate whether gut microbiota in early untreated PD may predictmotor and non-motor features progression over a 3-year period. Methods:16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients. Multiple confounders were taken into account, including dietary habits. Motor and non-motor symptoms were assessed using validated scales at baseline and followed-up yearly for 3 years. At last follow-up, a detailed neuropsychological assessment was additionally performed. A general linear model for repeated measurements— adjusted by dopaminergic therapy at follow-up— was used to investigate the relationship between bacterial taxa abundance at baseline (stratified by the median of distribution at baseline) and outcome variables. Results:Twenty-five patients were included (11 refused, 2 lost at follow-up, 1 died). Lower abundance of Roseburia (Firmicutes phylum) at baseline was associated with worse evolution of motor, non-motor and cognitive functions at 3-year follow-up. Similarly, lower abundance of Ruminococcaceae and Actinobacteria at baseline was associated with faster worsening of global cognitive functions. At follow-up, frontal lobe functions were the features most robustly associated with baseline microbial abnormalities. Conclusion:In the present exploratory study on de novo PD, we found an association between abnormal distribution of specific bacterial taxa and the progression of motor and non-motor features over a 3-year period. This proof-of-principle study supports the design of a larger observational study aiming to determine whether these differences survive multiple-comparison correction and define microbiota-specific subgroups suitable for therapeutic targeting.

中文翻译：

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肠道微生物群会影响帕金森病的进程吗？在新发患者中进行的为期 3 年的前瞻性探索性研究

背景：尽管肠道微生物群异常被认为会影响帕金森病 (PD) 的发病机制和临床表型，但缺乏对新发患者的前瞻性研究。目的：初步研究未经治疗的早期 PD 中的肠道微生物群是否可以预测 3 年期间运动和非运动特征的进展。方法：对 39 例新发 PD 患者的粪便样本进行 16S 核糖体 RNA 基因扩增。考虑了多种混杂因素，包括饮食习惯。运动和非运动症状在基线和每年随访 3 年中使用经过验证的量表进行评估。在最后一次随访时，还进行了详细的神经心理学评估。重复测量的一般线性模型（在随访时通过多巴胺能治疗进行调整）用于研究基线细菌类群丰度（由基线分布中位数分层）与结果变量之间的关系。结果：共纳入25例患者（拒绝11例，失访2例，死亡1例）。基线时较低丰度的 Roseburia (Firmicutes phylum) 与 3 年随访时运动、非运动和认知功能的更差演变相关。同样，基线时瘤胃球菌科和放线菌的丰度较低与整体认知功能的更快恶化有关。在随访中，额叶功能是与基线微生物异常最密切相关的特征。结论：在目前对 de novo PD 的探索性研究中，我们发现特定细菌分类群的异常分布与 3 年期间运动和非运动特征的进展之间存在关联。这项原理验证研究支持设计一项更大的观察性研究，旨在确定这些差异是否在多重比较校正后仍然存在，并定义适合治疗靶向的微生物群特异性亚组。