Causes and consequences of interpersonal microbial variation

人际微生物变异的原因和后果

• 批准号: 10621815
• 负责人: Andrew L Goodman
• 金额: $ 56.17万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-10 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621815
• 关键词: Animal Model; Area; Chemicals; Consumption; Diet; Environment; Evolution; Food; Future; Gastrointestinal tract structure; Genes; Genome; Germ-Free; Gnotobiotic; Goals; Health; Heterogeneity; Human; Human Biology; Human Genome; Individual; Investigation; Laboratories; Mass Spectrum Analysis; Measures; Mediating; Medical; Metabolism; Microbial Genetics; Molecular; Pharmaceutical Preparations; Phenotype; Process; Research; Shapes; Surveys; Variant; Xenobiotics; commensal microbes; disorder risk; drug metabolism; gut microbiome; gut microbiota; host microbiome; metabolomics; microbial; microbial community; microbiome; microbiome composition; microbiome research; programs; treatment response

Project Summary The human gastrointestinal tract harbors trillions of commensal microbes that collectively encode 150-fold more genes than the human genome; between individuals, microbiome variation far exceeds genome variation. Despite the possibility that the microbiome may represent a critical and readily modifiable component of human biology, the contribution of the gut microbiota to health, disease risk, and response to therapy remains largely undefined. The overall goal of our laboratory is to understand the principles, mechanisms, and processes that shape the interaction between gut microbial communities and their hosts. Our strategy is to combine anaerobic microbial genetics, high-throughput mass spectrometry, and gnotobiotic (germfree and ex- germfree) animal models to dissect these interactions. In recent studies, we have used these approaches to measure the contribution of the human gut microbiome to the metabolism of medical drugs and to define cooperative, competitive, and antagonistic processes in the gut microbiome. Our progress in these areas provides the basis for future studies centered on two themes. We will apply the metabolomic approaches we developed for studying microbiome-mediated drug metabolism to xenobiotic compounds that aren't drugs, including molecular components of food. Microbial genetic and gnotobiotic approaches also enable investigation of how two processes that are not readily measured in microbiome surveys, within-host evolution and phenotypic heterogeneity, contribute to host-microbiome interaction in the healthy and perturbed gut environment. If successful, these studies will define causes and consequences of host-microbiome interaction with broad implications for human health.

项目概要 人类胃肠道蕴藏着数万亿种共生微生物，它们共同编码了 150 倍 比人类基因组还多的基因；个体之间，微生物组变异远远超过基因组变异 变化。尽管微生物组可能代表一个关键且易于修改的组成部分 人类生物学、肠道微生物群对健康、疾病风险和治疗反应的贡献 很大程度上仍然是未定义的。我们实验室的总体目标是了解原理、机制和 塑造肠道微生物群落与其宿主之间相互作用的过程。我们的策略是 结合厌氧微生物遗传学、高通量质谱分析和无菌（无菌和前处理） 无菌）动物模型来剖析这些相互作用。在最近的研究中，我们使用这些方法 测量人类肠道微生物组对药物代谢的贡献并定义 肠道微生物组中的合作、竞争和拮抗过程。我们在这些领域的进展 为未来围绕两个主题的研究奠定了基础。我们将应用我们的代谢组学方法 开发用于研究微生物介导的药物代谢为非药物的异生化合物， 包括食物的分子成分。微生物遗传和无菌方法也使得 研究微生物组调查中不易测量的两个过程如何在宿主内进化 和表型异质性，有助于健康和紊乱肠道中宿主-微生物组的相互作用 环境。如果成功，这些研究将确定宿主-微生物组相互作用的原因和后果 对人类健康具有广泛的影响。