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.

抽象的 肠道微生物群落影响人类健康的多个方面，影响常见疾病，例如 肥胖、自身免疫性疾病和过敏。这些发现是通过应用实现的 对人类粪便样本进行宏基因组测序和质谱技术，取得了显着的成果 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，一个主要障碍 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患者护理环境 是获取、储存、处理和分析粪便样本的困难。挥发性有机化合物 (VOC) 存在于呼出的气体中，由许多微生物产生。通过耦合新方法 使用我们的无菌模型分析小鼠呼吸样本的 VOC 成分，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 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 肠道微生物群落的结构和功能。我们将通过以下方式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；和（2） 表征产生 VOC 的人类肠道微生物，并证明微生物产生的 VOC 存在于限生小鼠的呼吸中。我们的调查将很重要，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有了基本的了解，我们将开始 以确定特定的、个体挥发性微生物的相关性。因此，我们的工作将推出一个新的范式 开发新型非侵入性“呼吸分析仪”诊断方法来检查肠道微生物失调。