Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

中文翻译：

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帕金森病相关的肠道微生物组变化可预测疾病相关的代谢功能变化。

帕金森病（PD）是一种临床上定义为大脑中多巴胺能神经元变性的全身性疾病。虽然帕金森病中肠道微生物组组成的改变已被报道，但其功能后果仍不清楚。在此，我们通过对卢森堡帕金森氏症研究的粪便样本进行分析来解决这个问题（n = 147 例典型帕金森病病例，n = 162 例对照）。所有个体都接受了详细的临床评估，包括神经学检查和神经心理学测试，然后进行自我报告问卷调查。首先通过 16S rRNA 基因测序对这些人的粪便样本进行分析。其次，我们利用微生物组数据和人类肠道微生物的基因组规模代谢重建，通过个性化代谢模型预测了 129 种微生物代谢物的潜在分泌。我们的主要结果包括以下内容。PD 患者和健康对照之间的 8 个属和 7 个物种的相对丰度发生显着变化。PD 相关微生物模式在统计上取决于性别、年龄、体重指数和便秘。特别是，在控制疾病持续时间后，Bilophila 和 Paraprevotella 的相对丰度与 Hoehn 和 Yahr 分期显着相关。此外，肠道微生物群的个性化代谢模型揭示了帕金森病中九种微生物代谢物的预测分泌潜力中与帕金森病相关的代谢模式，包括增加的蛋氨酸和半胱氨酰甘氨酸。预测的微生物泛酸生产潜力与特定非运动症状的存在有关。我们的结果表明，与帕金森病相关的肠道微生物组的改变可以转化为影响宿主代谢和疾病表型的显着功能差异。