Elucidating the molecular and ecological design principles of stability and assembly of the human gut microbiota

阐明人类肠道微生物群稳定性和组装的分子和生态设计原理

• 批准号: 10054836
• 负责人: Ophelia Venturelli
• 金额: $ 1.07万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10054836
• 关键词: Antibiotics; Area; Bacteria; Behavior; Biological; Biology; Butyrates; Cells; Chemicals; Clostridium difficile; Communities; Complex; Computer Models; Ecology; Ecosystem; Expression Profiling; Gene Expression; Genetic; Genetic Determinism; Goals; Health; Homeostasis; Human; Lead; Maps; Mathematics; Measurement; Medicine; Metabolic; Modeling; Molecular; Nutrient; Phenotype; Physiology; Probiotics; Process; Property; Shapes; Structure; System; Work; colonization resistance; design; enteric pathogen; genome-wide; gut microbiome; gut microbiota; improved; member; microbial community; microbiome; pathogen; pressure; response

PROJECT SUMMARY The human gut microbiome is a dense ecosystem that collectively yields functions including diverse chemical transformations distributed among constituent community members and colonization resistance to intestinal pathogens that influences human physiology. A detailed and mechanistic understanding of the ecological and molecular forces that shape the assembly, activity and stability of the gut microbiota are largely unknown. Central to this problem is systematically mapping unknown inter-species interactions that realize emergent community-level properties and developing predictive computational models to describe ecosystem behaviors. We are developing a general framework to dissect the organization principles of the gut microbiota to pinpoint molecular mechanisms that shape community assembly and stability in response to environmental perturbations. Our general framework aims to decipher interactions among constituent members of a human gut microbiome synthetic ecology that mirrors the diversity of the natural system using measurements of lower- order assemblages to predict multi-species community behaviors. We will map ecological behaviors to molecules and genetic factors by elucidating gene expression profiles, single-cell phenotypes, genetic determinants of community structure and function and interrogating metabolic activities using genome-scale modeling. Leveraging these multifaceted approaches, we will investigate the principles of colonization resistance to C. difficile, ecological interactions that influence the stability and activity of butyrate-producing bacteria and molecular mechanisms that enable probiotics to realize stable ecological functions. Our work will ultimately lead to mathematical and biological principles that describe the complex behaviors of microbial communities to environmental pressures and will have profound impact across all areas of biology and medicine.

项目摘要 人肠道微生物组是一个密集的生态系统，共同产生包括不同化学物质的功能 在组成部分成员之间分布的转变和对肠道的殖民化抗性 影响人类生理的病原体。对生态和生态的详细和机械理解 塑造肠道菌群的组装，活性和稳定性的分子力在很大程度上未知。 这个问题的核心是系统地映射未知的种间交互，这些交互意识到了新兴 社区级的属性和开发预测性计算模型来描述生态系统行为。 我们正在开发一个通用框架，以剖析肠道菌群的组织原理以查明 响应环境的塑造社区组装和稳定性的分子机制 扰动。我们的一般框架旨在破译人的组成成员之间的互动 肠道微生物组综合生态学，通过测量较低的测量来反映自然系统的多样性 订单组合以预测多种物种社区行为。我们将将生态行为映射到 分子和遗传因子通过阐明基因表达谱，单细胞表型，遗传因素 社区结构和功能的决定因素，并使用基因组规模审问代谢活动 造型。利用这些多方面的方法，我们将研究殖民的原理 对艰难梭菌的抵抗力，影响产生丁酸酯的稳定性和活性的生态相互作用 使益生菌能够实现稳定的生态功能的细菌和分子机制。我们的工作将 最终导致数学和生物学原理描述微生物的复杂行为 对环境压力的社区，将在生物学的所有领域产生深远的影响 药品。