Interplay of diet and the metabolome in establishment of the juvenile gut microbi

饮食和代谢组在幼年肠道微生物建立中的相互作用

• 批准号: 8282260
• 负责人: John C Alverdy
• 金额: $ 21.12万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-15 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282260
• 关键词: Address; Adolescent; Affect; Bacteria; Behavior; Benign; Birth; Characteristics; Chemicals; Communities; Community Developments; Data; Databases; Development; Diet; Disease; Disease Outcome; Ecosystem; Environment; Feces; Formula Diets; Foundations; Future; Human; Human Milk; Incidence; Individual; Infant; Intervention; Intestines; Investigation; Lead; Life; Measures; Mediating; Metabolic; Metagenomics; Methodology; Microbe; Milk; Modality; Molecular; Molecular Analysis; Necrotizing Enterocolitis; Neonatal; Outcome; Play; Premature Infant; Prevention; Property; Protocols documentation; Research Personnel; Resolution; Role; Sampling; Scientist; Shapes; Structure; Taxon; Techniques; Time; Translating; Virulence; Virulent; Work; disorder control; feeding; gut microbiota; improved; metabolomics; metagenome; microbial; microbial community; microbiome; microorganism interaction; neonatal sepsis; neonate; novel strategies; premature; prevent; protective effect; small molecule; time interval

DESCRIPTION (provided by applicant): Our objective is to investigate the role of human breast milk and artificial formula in the recruitment, assembly, structuring and functioning of microbial communities in the premature gut. We hypothesize that the distinct intestinal chemical environment created by diet sets a trajectory towards establishment of microbial communities that differ between breast milk and formula fed infants thus explaining the "protective effect" of breast milk against microbe-mediated neonatal diseases, such as necrotizing enterocolitis. Enhancing our understanding of the relationship between diet and the succession of neonatal gut microbiota may eventually allow us to develop novel strategies to precisely manipulate the gut microbiota in order to control disease incidence and outcome. The basic study protocol involves daily stool sampling and molecular analysis of intestinal neonatal microbiota during the first few weeks following birth. This study protocol will allow us to track diet dependent succession of species leading to the establishment of distinct microbial assemblages in a high temporal resolution. We will use these colonization data to identify stable states of microbial communities for which we can use metagenomic techniques to study adaptation to the diet-dependent environment. Metagenomic data will also be used to compare the virulence potential of microbial communities. Finally, we will determine the metabolic footprint of major bacterial taxa and predict which metabolites have the potential to inhibit or enhance the bloom of each taxon. For each individual host, we will identify several time points when new species enter the intestinal ecosystem; these time points will be foci for metabolomic analyses to determine the flux of chemical components associated with species introductions. PUBLIC HEALTH RELEVANCE: Our objective is to investigate the role of human breast milk and artificial formula diets in the establishment of the neonatal gut microbiota. Serial stool samples will be used to study diet dependent microbial community dynamics and functional properties of microbiota from formula fed and milk fed neonates. We propose to determine a metabolic footprint of major bacterial taxa and suggest which metabolites are potentially able to inhibit or enhance the bloom of each taxon using a metabolomics approach.

描述（由申请人提供）：我们的目的是研究人类母乳和人工配方奶粉在早产儿肠道微生物群落的招募、组装、结构和功能中的作用。我们假设，饮食所创造的独特的肠道化学环境设定了一个轨道，建立母乳和配方奶粉喂养的婴儿之间不同的微生物群落，从而解释了母乳对微生物介导的新生儿疾病，如坏死性小肠结肠炎的“保护作用”。加强我们对饮食与新生儿肠道微生物群演替之间关系的理解，最终可能使我们能够开发新的策略来精确操纵肠道微生物群，以控制疾病的发病率和结果。 基础研究方案包括在出生后的前几周内每天进行粪便采样和肠道新生儿微生物群的分子分析。本研究方案将 使我们能够跟踪饮食依赖的物种演替，从而以高时间分辨率建立不同的微生物组合。我们将使用这些定殖数据来确定微生物群落的稳定状态，我们可以使用宏基因组技术来研究对饮食依赖环境的适应。宏基因组数据还将用于比较微生物群落的毒力潜力。最后，我们将确定主要细菌分类群的代谢足迹，并预测哪些代谢产物有可能抑制或增强每个分类群的水华。对于每个个体宿主，我们将确定新物种进入肠道生态系统的几个时间点;这些时间点将是代谢组学分析的焦点，以确定与物种引入相关的化学成分的通量。 公共卫生相关性：我们的目标是研究母乳和人工配方饮食在建立新生儿肠道菌群中的作用。连续粪便样本将用于研究配方奶粉喂养和牛奶喂养的新生儿的饮食依赖性微生物群落动态和微生物群的功能特性。我们建议确定主要细菌类群的代谢足迹，并建议哪些代谢物可能能够抑制或增强使用代谢组学方法的每个类群的水华。