多组学分析帕金森病中的肠道菌群组成和功能
  • 帕金森病(PD)患者的粪便菌群和代谢组的组成,与健康人显著不同;
  • PD中发生改变的粪便代谢物及其相关功能包括:有潜在神经保护作用的生物活性分子(如SCFA、辅酶Q和水杨酸),以及与神经退行性变有关的分子(如神经酰胺、鞘氨醇和TAMO);
  • PD组中,认知损伤、低BMI、虚弱、便秘和少身体活动与粪便代谢组的组成差异相关,其中低SCFA与较差的认知和低BMI相关,低丁酸水平与更差的姿势不稳定步态障碍相关。
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mildbreeze
不少研究表明,帕金森病(PD)患者存在肠道菌群改变,但其与疾病的功能性关联尚不清楚。Annals of Neurology近期发表的一项研究,纳入了104名帕金森病(PD)患者和96名对照个体,详细分析了PD中的粪便微生物组和代谢组的改变,及其与患者临床表型的关联,揭示了PD相关菌群的代谢功能变化与PD发生发展的密切关系,表明特定的肠道菌群代谢物或可作为PD的标志物和治疗靶点。
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Gut microbial ecosystem in Parkinson's disease: New clinico‐biological insights from multi‐omics

帕金森病中的肠道微生物生态系统:来自多组学的临床生物学新洞见

10.1002/ana.25982

2020-12-03, Article

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Objectives: Gut microbiome alterations in Parkinson's disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.
Methods: Two‐hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analysed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography‐mass spectrometry.
Results: Fecal microbiome and metabolome composition in PD were significantly different vs. controls, with the largest effect size seen in NMR‐based metabolome. Microbiome and NMR‐based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD vs. controls included bioactive molecules with putative neuroprotective effects (e.g., short chain fatty acids [SCFAs], ubiquinones, and salicylate), and other compounds increasingly implicated in neurodegeneration (e.g., ceramides, sphingosine, and trimethylamine N‐oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability‐gait disorder scores.
Interpretation: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut‐brain pathophysiology. Their clinical relevance further supports a role for microbial‐metabolites as potential targets for the development of new biomarkers and therapies in PD.

First Authors:
Ai Huey Tan

Correspondence Authors:
Ai Huey Tan,Chun Wie Chong

All Authors:
Ai Huey Tan,Chun Wie Chong,Shen-Yang Lim,Ivan Kok Seng Yap,Cindy Shuan,Ju Teh,Mun Fai Loke,Sze-Looi Song,Jiun Yan Tan,Ban Hong Ang,Yong Qi Tan,Mee Teck Kho,Jeff Bowman,Sanjiv Mahadeva,Hoi Sen Yong,Anthony E Lang

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