Impact of gut microbial metabolism on host breath volatiles

肠道微生物代谢对宿主呼吸挥发物的影响

• 批准号: 10625451
• 负责人: Ariel Jose Hernandez-Leyva
• 金额: $ 2.67万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2023-07-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10625451
• 关键词: 16S ribosomal RNA sequencing; Affect; Animals; Asthma; Bacteria; Bacterial DNA; Biological Markers; Blood; Chairperson; Clinic; Clinical; Clinical Research; Collaborations; Collection; Communities; DNA sequencing; Data; Diagnostic; Disease; Ensure; Environment; Excretory function; Exhalation; Feces; Future; Genes; Germ-Free; Gnotobiotic; Health; Heterogeneity; Human; Human Microbiome; Inflammatory Bowel Diseases; Institution; Investigation; Laboratories; Laboratory Finding; Liquid substance; Malaria; Mammals; Mass Fragmentography; Measures; Mentorship; Metabolic; Metabolism; Metagenomics; Methods; Microbe; Mus; Neurodegenerative Disorders; Obesity; Patients; Phase; Physicians; Prognosis; Refrigeration; Research; Sampling; Scientist; Shotguns; Site; Source; Sterility; Testing; Time; Tissues; Training; Translating; Universities; Urine; Volatilization; Washington; Work; absorption; antimicrobial; bacterial metabolism; biomarker identification; clinical application; clinically relevant; diagnostic biomarker; experimental study; gut bacteria; gut microbes; gut microbiome; gut microbiota; host-microbe interactions; humanized mouse; inter-individual variation; metabolomics; metagenome; metagenomic sequencing; microbial; microbial community; microbial products; microbiome; microbiome composition; microbiome research; microbiota; microbiota profiles; microbiota transplantation; mouse model; pressure; prognostic; quorum sensing; stool sample; vapor; volatile organic compound

Project Summary/Abstract The gut microbiome has been implicated in various diseases such as inflammatory bowel disease, asthma, and neurodegenerative diseases. Despite the progress made in the studies of these diseases, there remains remarkable heterogeneity in patient presentation and prognosis. The interindividual variability in gut microbiome composition and metabolic functions may in part explain the interindividual variability in disease. Characterization of the gut microbiome is typically carried out using metagenomic sequencing or marker gene sequencing of the V4 16S sequence of bacteria in stool; however, these methods are not always possible in a clinical setting. Human stool must be acquired, properly stored, and is often not readily available at the site and time of collection for a clinical study. Metabolomic analysis of stool or urine also provides information about the functions of the bacteria present in the gut microbiome, however there is yet an even more convenient sample that carries information relevant to human health. In this project I propose to investigate the breath volatile profile as a medium for characterizing the gut microbiome. There are over 800 volatile organic compounds (VOC) that have been detected in human breath, some of them unexplained by host cellular metabolism. I hypothesize that the gut microbiota contributes otherwise unexplained VOCs to the host breath VOC profile. In Specific Aim 1 I will characterize the breath VOC profile of gnotobiotic mice to test the effect of gut microbiome composition on the breath VOC profile. In Specific Aim 2 I will show that bacterial metabolism directly produces VOCs that are absorbed by the host and excreted in breath with a monocolonized gnotobiotic mouse model. Finally, in Specific Aim 3, I will determine the effect of the microbiome on human breath by comparing the results of metagenomic sequencing of human stool with human breath VOCs collected as part of a recently completed clinical study. This investigation will take place at Washington University in St. Louis, a renowned institution for microbiome research, in the laboratory of Dr. Andrew Kau, an expert in the study of the microbiome and its interactions with the host. To supplement my training and expertise, I will collaborate with the laboratory of Dr. Audrey Odom- John, an expert in breath volatile profiling. Further supporting my mentorship team, Dr. Gautam Dantas will provide excellent advice as a co-sponsor and the chairperson of my thesis committee. This excellent training environment will ensure the research plan proposed provides rigorous scientific training for me as future physician-scientist.

项目总结/摘要 肠道微生物组与各种疾病有关，例如炎症性肠病、哮喘和哮喘。 神经退行性疾病尽管对这些疾病的研究取得了进展， 患者表现和预后的显著异质性。肠道微生物组的个体间差异 组成和代谢功能可以部分解释疾病的个体间差异。表征 通常使用肠道微生物组的宏基因组测序或标记基因测序来进行肠道微生物组的鉴定。 粪便中细菌的V4 16 S序列;然而，这些方法在临床环境中并不总是可行的。 人粪便必须获得，适当储存，并且在收集地点和时间通常不容易获得 进行临床研究粪便或尿液的代谢组学分析还提供了关于代谢酶的功能的信息。 细菌存在于肠道微生物组中，然而，还有一种更方便的样品， 与人类健康有关的信息。在这个项目中，我建议调查的呼吸挥发性档案作为一个 用于表征肠道微生物组的培养基。有超过800种挥发性有机化合物（VOC）， 在人类呼吸中检测到，其中一些无法用宿主细胞代谢来解释。我假设 肠道微生物群对宿主呼吸VOC谱贡献了其他无法解释的VOC。具体目标1 我将描述知菌小鼠的呼吸VOC特征，以测试肠道微生物组组成对小鼠呼吸的影响。 呼吸VOC曲线。在具体目标2中，我将展示细菌代谢直接产生挥发性有机化合物， 通过单菌落的知菌小鼠模型，被宿主吸收并通过呼吸排出。最后，具体 目的3，通过比较宏基因组学的结果，确定微生物组对人类呼吸的影响。 作为最近完成的临床研究的一部分收集的具有人呼吸VOC的人粪便的测序。 这项调查将在圣路易斯的华盛顿大学进行，这是一所著名的微生物研究所 研究，在安德鲁·考博士的实验室，在微生物组及其相互作用的研究专家， 主持人为了补充我的训练和专业知识，我将与奥德丽·奥多姆博士的实验室合作- 约翰，呼吸挥发物分析专家。为了进一步支持我的导师团队，Gautam Dantas博士将 作为共同赞助人和我的论文委员会主席，我提供了很好的建议。这种优秀的培训 环境将确保拟议的研究计划为我提供严格的科学培训， 物理学家兼科学家

项目成果

The gut metagenome harbors metabolic and antibiotic resistance signatures of moderate-to-severe asthma.

肠道宏基因组具有中度至重度哮喘的代谢和抗生素耐药性特征。

• DOI: 10.1101/2023.01.03.522677
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Wilson,NaomiG;Hernandez-Leyva,Ariel;Schwartz,DrewJ;Bacharier,LeonardB;Kau,AndrewL
• 通讯作者: Kau,AndrewL