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基于质谱的代谢组学:靶向神经退行性疾病中肠道微生物群和大脑的串扰。

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

机构信息

Department of Chemistry, Hong Kong Baptist University, Kowloon Tong, Hong Kong SAR, China.

Key Laboratory of Analytical Chemistry of State Ethnic Affairs Commission, College of Chemistry and Materials Science, South-Central University for Nationalities, Wuhan, Hubei, China.

出版信息

Mass Spectrom Rev. 2019 Jan;38(1):22-33. doi: 10.1002/mas.21553. Epub 2017 Nov 12.

DOI:10.1002/mas.21553
PMID:29130504
Abstract

Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the investigation of underlying mechanism of therapeutic strategies.

摘要

代谢组学旨在通过遗传或环境变化对生物系统进行“快照”,以获取所有小分子代谢物的水平、活性、调节和相互作用的信息。质谱技术的新兴发展在发现和定量与肠道微生物群和大脑相关的神经活性小分子代谢物方面显示出了希望。最近在与神经发育和神经退行性疾病相关的小分子代谢物的中间作用的特征方面取得了重大进展,表明其在理解肠道微生物群和宿主大脑之间的串扰方面具有潜力。更多的证据表明,小分子代谢物可能在介导微生物对神经传递和疾病发展的影响方面发挥关键作用。基于质谱的代谢组学非常适合获取肠道微生物群和大脑之间双向通讯中的代谢信号。在这篇综述中,我们总结了主要的质谱技术,包括液相色谱-质谱、气相色谱-质谱和成像质谱,用于神经退行性疾病的代谢组学研究。我们还回顾了通过质谱鉴定新代谢物和涉及肠道微生物群与大脑连接的代谢途径的最新进展。这些代谢途径允许微生物群影响大脑的正常功能,而大脑反过来又可以通过神经递质物质影响微生物群的组成。这种串扰的功能失调相互作用将帕金森病、阿尔茨海默病和亨廷顿病等神经退行性疾病联系起来。基于质谱的代谢组学分析为靶向神经退行性疾病中小分子代谢物的功能失调途径提供了信息,这可能对研究治疗策略的潜在机制具有重要价值。

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