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

基本信息

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
项目类别：
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

项目摘要

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）：我们的目标是研究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。我们假设饮食创造的独特肠道化学环境设定了建立母乳和配方奶喂养婴儿之间不同的微生物群落的轨迹，从而解释了母乳对微生物介导的新生儿疾病（例如坏死性小肠结肠炎）的“保护作用”。增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出新的策略来精确控制肠道微生物群，从而控制疾病的发生和结果。基本研究方案包括在出生后最初几周内每日进行粪便取样和对新生儿肠道微生物群进行分子分析。本研究方案将让我们能够追踪物种的饮食依赖性演替，从而以高时间分辨率建立独特的微生物组合。我们将利用这些定植数据来确定微生物群落的稳定状态，我们可以利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类群的代谢足迹，并预测哪些代谢物有可能抑制或增强每个类群的繁殖。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；这些时间点将成为代谢组学分析的重点，以确定与物种引入相关的化学成分的通量。公共健康相关性：我们的目标是研究母乳和人工配方食品在新生儿肠道微生物群建立中的作用。系列粪便样本将用于研究饮食依赖性微生物群落动态以及配方奶喂养和牛奶喂养新生儿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，并使用代谢组学方法建议哪些代谢物可能能够抑制或增强每个类群的繁殖。