Comprehensive Profiling of Fecal Metabolome of Mice by Integrated Chemical Isotope Labeling-Mass Spectrometry Analysis
Comprehensive Profiling of Fecal Metabolome of Mice by Integrated Chemical Isotope Labeling-Mass Spectrometry Analysis
复制标题
通过化学同位素标记-质谱综合分析对小鼠粪便代谢组进行综合分析
DOI：
10.1021/acs.analchem.7b05355
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发表时间：
2018-03-06
影响因子：
7.4
通讯作者：
Feng, Yu-Qi
中科院分区：
文献类型：
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作者：
Yuan, Bi-Feng;Zhu, Quan-Fei;Feng, Yu-Qi
肠道微生物群在宿主健康中发挥着重要作用。宿主和共生肠道微生物群在食物和外源物质的代谢过程中共同产生大量代谢物。粪便代谢物的分析可以提供一种非侵入性的方式来研究宿主-肠道微生物群相互作用的结果。在此，我们报告了通过集成化学同位素标记结合液相色谱质谱（CIL-LC-MS）分析对小鼠粪便代谢组进行的全面分析。根据功能部分（即羧基、羰基、胺和硫醇）将代谢物分为几个亚代谢组，然后对各个亚代谢组进行分析。来自亚代谢组的组合数据形成覆盖率相对较高的代谢组。为此，我们合成了稳定的同位素标记试剂来标记不同基团的代谢物，包括羧基、羰基、胺基和硫醇基团。我们检测到 2302 种潜在代谢物，其中 1388 种在小鼠粪便中可以被阳性或推定鉴定。然后，我们根据我们建立的化学标记标准品库和串联质谱分析进一步确认了 308 种代谢物。利用已鉴定的小鼠粪便中的代谢物，我们建立了小鼠粪便代谢组数据库，可用于轻松鉴定小鼠粪便中的代谢物。此外，我们发现211种粪便代谢物在阿尔茨海默病（AD）模型小鼠和野生型（WT）小鼠之间表现出显着差异，这表明粪便代谢物与AD病理之间存在密切相关性，并为AD的诊断提供新的潜在生物标志物。
Gut microbiota plays important roles in the host health. The host and symbiotic gut microbiota coproduce a large number of metabolites during the metabolism of food and xenobiotics. The analysis of fecal metabolites can provide a noninvasive manner to study the outcome of the host-gut microbiota interaction. Herein, we reported the comprehensive profiling of fecal metabolome of mice by an integrated chemical isotope labeling combined with liquid chromatography mass spectrometry (CIL-LC-MS) analysis. The metabolites are categorized into several submetabolomes based on the functional moieties (i.e., carboxyl, carbonyl, amine, and thiol) and then analysis of the individual submetabolome was performed. The combined data from the submetabolome form the metabolome with relatively high coverage. To this end, we synthesized stable isotope labeling reagents to label metabolites with different groups, including carboxyl, carbonyl, amine, and thiol groups. We detected 2302 potential metabolites, among which, 1388 could be positively or putatively identified in feces of mice. We then further confirmed 308 metabolites based on our established library of chemically labeled standards and tandem mass spectrometry analysis. With the identified metabolites in feces of mice, we established mice fecal metabolome database, which can be used to readily identify metabolites from feces of mice. Furthermore, we discovered 211 fecal metabolites exhibited significant difference between Alzheimer's disease (AD) model mice and wild type (WT) mice, which suggests the close correlation between the fecal metabolites and AD pathology and provides new potential biomarkers for the diagnosis of AD.