Characterizing the Metabolome and Volatilome of Gut Microbiome

项目概要： 先前的研究表明，微生物代谢产物通常是体内变化最显着的化合物 当比较患病与健康个体时的疾病状态。最近的研究还表明， 微生物转化食物成分产生的代谢产物对宿主有显著影响 生理过程，如能量代谢、肠道和免疫稳态、神经行为，以及 血管功能此外，有人提出，代谢组学指导的功能干预， 外源性代谢物在细胞活动中可能发挥重要的生物学作用。然而，没有现有的， 详细的，定量的技术，用于测量广泛的内源性微生物 代谢物，也没有系统的调查微生物群落的代谢 功能协调发展的为了填补现有的知识空白，本提案中概述的研究计划侧重于三个方面 核心领域：1）发展先进的基于质谱的代谢组学技术， 肠道微生物代谢产物的检测和广泛覆盖; 2）开发二次电喷雾电离- 场不对称波形离子迁移谱-高分辨率质谱（SESI-FAIMS- HRMS）用于肠道微生物挥发性有机化合物的快速检测; 3）利用现有的 从我们的合作者的实验室的样品，以验证我们的代谢组学方法，并阐明的功能， 儿茶素类在肥胖宿主体内的微生物代谢产物。这三个连贯的领域集中在发展和 基于质谱的代谢组学、挥发物组学和相关微生物生物技术工具的应用 以实现微生物代谢和营养-肠道微生物组-宿主相互作用的功能研究。我们认为 这项研究计划在阐明微生物代谢物对宿主健康的影响方面具有巨大的潜力， 疾病，并提供用于调节这些代谢物以实现全部治疗潜力的指南， 以及用于靶向微生物代谢以促进人类健康。

Project Summary: Previous studies have shown that microbial metabolites are often the compounds most markedly altered in the disease state when comparing diseased versus healthy individuals. Recent studies also suggest that metabolites deriving from microbial transformation of dietary components have significant effects on host physiological processes such as energy metabolism, gut and immune homeostasis, neurological behavior, and vascular function. Additionally, it has been proposed that metabolomics-directed functional interventions using exogenous metabolites may play critical biological roles in cellular activities. However, there are no existing, detailed, and quantitative techniques for the measurement of a broad range of endogenous microbial metabolites, nor has there been a systematic investigation of microbial communities for their metabolic functions. To fill the existing gap of knowledge, the research program outlined in this proposal focuses on three core areas: 1) Develop advanced mass spectrometry-based metabolomics technique for sensitive, quantitative detection and broad coverage of gut microbial metabolites; 2) Develop Secondary Electrospray Ionization – Field Asymmetric Waveform Ion Mobility Spectrometry – High-Resolution Mass Spectrometry (SESI-FAIMS- HRMS) for the rapid detection of gut microbial volatile organic compound detection; 3) Utilizing existing samples from our collaborator's lab to validate our metabolomics methods and elucidate the functionality of catechins microbial metabolites in obese host. These three coherent areas center on the development and application of mass spectrometry-based metabolomics, volatilomics and related microbial biotechnology tools to enable functional studies of microbial metabolism and nutrition-gut microbiome-host interactions. We believe this research program has great potential to elucidate the impact of microbial metabolites on host health and diseases, and to provide guidelines for modulating these metabolites to realize the full therapeutic potential, and for targeting microbial metabolism to promote human health.