Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral & Craniofacial Sciences, King's College London, SE1 9RT London, UK.
Department of Neurology, University Hospital Bonn, Venusberg Campus 1, 53127 Bonn, Germany; Gut Microbes & Health, Quadram Institute Bioscience, Norwich Research Park, Norwich, Norfolk NR4 7UA, UK.
Cell Rep. 2021 Mar 2;34(9):108807. doi: 10.1016/j.celrep.2021.108807.
Parkinson's disease (PD) is the most common progressive neurological disorder compromising motor functions. However, nonmotor symptoms, such as gastrointestinal (GI) dysfunction, precede those affecting movement. Evidence of an early involvement of the GI tract and enteric nervous system highlights the need for better understanding of the role of gut microbiota in GI complications in PD. Here, we investigate the gut microbiome of patients with PD using metagenomics and serum metabolomics. We integrate these data using metabolic modeling and construct an integrative correlation network giving insight into key microbial species linked with disease severity, GI dysfunction, and age of patients with PD. Functional analysis reveals an increased microbial capability to degrade mucin and host glycans in PD. Personalized community-level metabolic modeling reveals the microbial contribution to folate deficiency and hyperhomocysteinemia observed in patients with PD. The metabolic modeling approach could be applied to uncover gut microbial metabolic contributions to PD pathophysiology.
帕金森病（PD）是最常见的进行性神经退行性疾病，会损害运动功能。然而，胃肠道（GI）功能障碍等非运动症状先于影响运动的症状出现。胃肠道和肠神经系统早期受累的证据强调了需要更好地了解肠道微生物群在 PD 胃肠道并发症中的作用。在这里，我们使用宏基因组学和血清代谢组学研究 PD 患者的肠道微生物组。我们使用代谢建模整合这些数据，并构建一个综合相关网络，深入了解与疾病严重程度、GI 功能障碍和 PD 患者年龄相关的关键微生物物种。功能分析显示，PD 中微生物降解粘蛋白和宿主糖的能力增强。个性化社区级代谢建模揭示了微生物对 PD 患者中观察到的叶酸缺乏和高同型半胱氨酸血症的贡献。这种代谢建模方法可用于揭示肠道微生物代谢对 PD 病理生理学的贡献。
