Microbial Origin of Breath Volatile Metabolites

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。这些发现是通过应用 人类粪便样本的超基因组测序和质谱学技术，导致显著 洞察肠道微生物群落与人类健康之间的相互作用。然而，一个主要的障碍是 将我们不断增长的关于肠道微生物区系及其功能的知识转化到患者护理环境中 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 (VOCs)存在于呼气中，由许多微生物产生。通过结合一种新的方法 用我们的灵知生菌模型分析小鼠呼气样本的VOC组成，我们发现呼气VOC 模式反映了肠道微生物群落。根据这一初步数据，我们的中心假设是 呼吸中观察到的许多VOCs是由肠道微生物区系产生的，因此代表着 肠道微生物群落结构和功能。我们将通过以下几点来验证我们的中心假设 具体目标：(1)评估肠道微生物群落影响呼吸VOC谱的程度；以及(2) 描述产生VOCs的人类肠道微生物的特征并证明微生物产生的VOCs 存在于灵知生菌小鼠的呼吸中。我们的调查将具有重大意义，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了解，我们将开始 以确定特定的、个体挥发性与微生物的相关性。因此，我们的工作将启动一种新的范式 新的，非侵入性的“呼气测定仪”诊断，以询问肠道微生物失调。

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.