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

描述(由申请人提供)：我们的目标是调查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，饮食创造的独特的肠道化学环境设定了一条建立不同于母乳和配方奶婴儿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的“保护作用”，如坏死性小肠结肠炎。加强我们对饮食和新生儿肠道微生物区系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地操纵肠道微生物区系，以控制疾病的发病率和预后。 基本研究方案包括每日大便采样和新生儿出生后头几周肠道微生物区系的分子分析。这项研究方案将 使我们能够追踪依赖饮食的物种演替，从而以高时间分辨率建立不同的微生物组合。我们将使用这些定植数据来确定微生物群落的稳定状态，为此我们可以使用元基因组学技术来研究对依赖饮食的环境的适应。元基因组数据也将被用来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，并预测哪些代谢物有可能抑制或促进每个分类群的开花。对于每个单独的宿主，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分析的重点，以确定与物种引入相关的化学成分的流量。 公共卫生相关性：我们的目标是调查人类母乳和人工配方饮食在建立新生儿肠道微生物区系中的作用。将使用系列粪便样本来研究配方奶喂养和母乳喂养的新生儿的依赖饮食的微生物群落动态和微生物区系的功能特性。我们建议确定主要细菌分类群的代谢足迹，并使用代谢组学方法建议哪些代谢物能够潜在地抑制或促进每个分类群的开花。

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.