Characterizing the Metabolome and Volatilome of Gut Microbiome

项目总结： 以前的研究表明，微生物代谢物往往是在 在比较患病个体和健康个体时的疾病状态。最近的研究还表明， 日粮成分微生物转化产生的代谢物对宿主有显著影响 生理过程，如能量代谢、肠道和免疫动态平衡、神经行为和 血管功能。此外，已经提出代谢组学指导的功能干预使用 外源代谢物可能在细胞活动中发挥关键的生物学作用。然而，没有现有的， 用于测量范围广泛的内源微生物的详细和定量技术 代谢物，也没有对其代谢的微生物群落进行系统调查 功能。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)开发先进的基于质谱学的代谢组学技术，用于敏感、定量 肠道微生物代谢物的检测和广泛覆盖；2)发展二次电喷雾电离- 场不对称波形离子迁移率谱-高分辨质谱学 HRMS)用于肠道微生物挥发性有机物的快速检测；3)利用现有的 来自我们合作者实验室的样本来验证我们的代谢组学方法并阐明 肥胖宿主体内儿茶素微生物代谢产物的研究。这三个连贯的领域集中在发展和 基于质谱学的代谢组学、挥发性组学及相关微生物生物技术工具的应用 使微生物代谢和营养-肠道微生物-宿主相互作用的功能研究成为可能。我们相信 这项研究计划具有很大的潜力来阐明微生物代谢物对宿主健康和 并为调节这些代谢物以实现充分的治疗潜力提供指南， 并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.