Microbial Origin of Breath Volatile Metabolites

呼吸挥发性代谢物的微生物来源

• 批准号: 10043038
• 负责人: Andrew Leon Kau
• 金额: $ 26.45万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10043038
• 关键词: Anaerobic Bacteria; Animal Husbandry; Asthma; Autoimmune Diseases; Bacteria; Bedside Testings; Bile Acids and Salts; Biological; Biological Markers; Breath Tests; Chemical Structure; Clinical; Collection; Communicable Diseases; Coupling; Data; Diagnostic; Diagnostic tests; Disease; Ecology; Ensure; Exhalation; Genes; Germ-Free; Gnotobiotic; Health; Human; Hypersensitivity; In Vitro; Individual; Investigation; Knowledge; Lung; Malignant Neoplasms; Mass Spectrum Analysis; Mediating; Metabolic; Metagenomics; Methods; Microbe; Modeling; Mus; Obesity; Output; Participant; Patient Care; Pattern; Reproducibility; Research; Sampling; Shapes; Techniques; Testing; Time; Translating; Volatile Fatty Acids; Work; base; breath composition; dysbiosis; experience; gut bacteria; gut microbes; gut microbiota; immune function; improved; innovation; insight; lipophilicity; metagenomic sequencing; microbial; microbial community; microbiota; novel; novel therapeutics; point-of-care diagnostics; pressure; success; tool; vapor; volatile organic compound

ABSTRACT Gut microbial communities influence multiple facets of human health, impacting common disorders such as obesity, autoimmune diseases, and allergies. These discoveries were enabled by the application of metagenomic sequencing and mass spectrometric techniques to human fecal samples, leading to remarkable insights into the interplay between gut microbial communities and human health. However, a major barrier to translating our growing knowledge about the gut microbiota and its functions to the patient-care setting is the difficulty in obtaining, storing, processing and analyzing fecal samples. Volatile organic compounds (VOCs) are present in exhaled breath and are produced by many microbes. By coupling a new method for analyzing the VOC composition of mouse breath samples with our gnotobiotic model, we find that breath VOC patterns reflect the gut microbial communities. Based on this preliminary data, our central hypothesis is that many VOCs observed in breath are produced by the gut microbiota and thus represent biomarkers of gut microbial community configuration and function. We will test our central hypothesis through the following specific aims: (1) Evaluate the extent to which gut microbial communities shape breath VOC profiles; and (2) Characterize human gut microbes that generate VOCs and demonstrate that microbe-produced VOCs are present in the breath of gnotobiotic mice. Our investigations will be significant, because we will greatly advance our fundamental understanding of the gut microbial contribution to breath volatile composition, and we will begin to identify specific, individual volatile-microbe correlations. Our work will therefore launch a new paradigm towards novel, non-invasive “breathalyzer” diagnostics to interrogate gut microbial dysbiosis.

摘要 肠道微生物群落影响人类健康的多个方面，影响常见疾病，如 肥胖自身免疫性疾病和过敏症这些发现是通过应用 宏基因组测序和质谱技术对人类粪便样本，导致显着 深入了解肠道微生物群落与人类健康之间的相互作用。然而， 将我们不断增长的关于肠道微生物群及其功能的知识转化为病人护理环境 粪便样本的获取、储存、处理和分析困难。挥发性有机化合物 挥发性有机化合物（VOC）存在于呼出气体中，由许多微生物产生。通过结合一种新的方法， 用我们的知菌模型分析小鼠呼吸样品的VOC组成，我们发现呼吸VOC 模式反映了肠道微生物群落。根据这些初步数据，我们的中心假设是， 在呼吸中观察到的许多VOC是由肠道微生物群产生的，因此代表了 肠道微生物群落结构和功能。我们将通过以下内容来检验我们的中心假设 具体目标：（1）评估肠道微生物群落对呼吸VOC特征的影响程度;以及（2） 表征产生VOC的人类肠道微生物，并证明微生物产生的VOC是 存在于知菌鼠的呼吸中。我们的调查将是重要的，因为我们将大大推进 我们对肠道微生物对呼吸挥发性成分的贡献的基本理解，我们将开始 以确定特定的、个体的挥发物与微生物的相关性。因此，我们的工作将启动一个新的范例， 迈向新型、非侵入性的“呼气测醉器”诊断，以探究肠道微生物生态失调。