Resilience in early development: How antibiotics shape infant microbiome assembly

早期发育的弹性：抗生素如何塑造婴儿微生物组组装

基本信息

批准号：
8704976
负责人：
Elizabeth Costello
金额：
$ 10.46万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-25 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8704976
关键词：
Acute Adult Affect Age Age-Years Amoxicillin Antibiotic Resistance Antibiotic Therapy Antibiotics Asthma Bacteria Bacteriophages Bacteroides Bifidobacterium Birth Child Child health care Childhood Asthma Chronic Clostridium difficile Colitis Collection Communities Complex Contracts DNA Data Development Diarrhea Disease Distal Elements Environment Exhibits Feces Fetal Development Food Gastrointestinal tract structure Generations Genes Genetic Genome Genomics Goals High-Throughput Nucleotide Sequencing Human Human Development Immigration Immune system In Situ Indigenous Individual Infant Infection Inflammatory Bowel Diseases Internet Intestines Klebsiella Knowledge Life Link Mediating Metabolism Metagenomics Methods Microbe Mothers Obesity Oral Oral cavity Pattern Phylogenetic Analysis Plasmids Population Postpartum Period Process Recording of previous events Recovery Research Resistance Resolution Sampling Series Shapes Shotgun Sequencing Site Skin Solid Source Structure Surveys Taxon Testing Time Time Series Analysis Tooth structure Vagina Variant Vertical Disease Transmission Work base cohort early childhood functional genomics human disease immune function imprint infant nutrition metagenomic sequencing microbial colonization microbial community microbiome nutrition obesity risk pathogen postnatal predictive modeling programs public health relevance rRNA Genes resilience response transmission process

项目摘要

DESCRIPTION (provided by applicant): Fetal development generally takes place within a microbe-free environment. During delivery and rapidly thereafter, microbes from a variety of sources colonize the infant skin, mouth, and gastrointestinal tract until dense, complex communities are established. Successional changes in the structure and function of these communities are marked in early development and have important consequences for infant nutrition, pathogen resistance, gut maturation, and immune system programming. During this time, deviations from the normal development of the indigenous microbiota may affect child health. Antibiotic disruption of the native microbiota is implicated in a wide range of human disease, including Clostridium difficile colitis and other acute and chronic forms of diarrhea. Longer-term consequences, such as childhood asthma, obesity, and inflammatory bowel disease have also been linked to antibiotic use early in life. Surprisingly, we lack a clear understanding of the direct effects of antibiotics on the developing microbiota of infants. In part this is because until recently, methods capable of detecting the signature of disturbance within complex, dynamic microbial communities were unavailable. Albeit an integral and universal part of human development, the postnatal assembly of the indigenous microbiota, including its variability over time, sources of colonists, responses to disturbance, and the key factors affecting such patterns remains poorly understood. Our objective is to track microbiome assembly from birth until two years of age in a cohort of 20 healthy infants, by following baseline developmental patterns and responses to antibiotic perturbation using time series analysis of high-throughput phylogenetic marker gene and metagenomic sequencing surveys. We will also track the postpartum microbiomes of their mothers, and assess the evidence for direct transmission from mother to child. We hypothesize that the developing microbiomes of infants exhibit resilience in the wake of antibiotic therapy. Having examined this question, we will go on to test the specific hypothesis that the response of the developing microbiome to antibiotic exposure depends, in part, on the infant's mode of delivery. We will study this question in a larger cohort of amoxicillin-treated infants. The long-term goal of this research is to understand the ecological basis of microbiome resilience (or collapse) in the context of early childhood development. It will lay important groundwork for predictive models of antibiotic (or other) perturbation responses that will aid in the promotion of healthy microbiome transmission and assembly.

描述（由申请人提供）：胎儿发育通常发生在无微生物环境中。在分娩期间，此后迅速，来自各种来源的微生物将婴儿的皮肤，口腔和胃肠道定居直至建立茂密的社区。这些社区的结构和功能的演替变化在早期发展中标记，并对婴儿营养，病原体抗性，肠道成熟和免疫系统编程产生重要影响。在此期间，与土著菌群正常发育的偏差可能会影响儿童健康。天然微生物群的抗生素破坏与广泛的人类疾病有关，包括艰难梭菌结肠炎以及其他急性和慢性腹泻形式。长期后果，例如儿童哮喘，肥胖和炎症性肠病，也与生命早期的抗生素使用有关。令人惊讶的是，我们对抗生素对婴儿发育中的菌群的直接影响缺乏清晰的了解。这部分是因为直到最近，还无法检测复杂的动态微生物群落中干扰特征的方法。尽管是人类发展的不可或缺和普遍的一部分，但土著微生物群的产后组装，包括其在时间上的变异性，殖民者的来源，对干扰的反应以及影响此类模式的关键因素仍然很众所周知。我们的目的是通过遵循基线来跟踪从出生到两岁的微生物组装，直到两岁发育模式和对抗生素扰动的反应，使用高通量系统发育标记基因和元基因组测序调查的时间序列分析。我们还将跟踪母亲的产后微生物，并评估直接传播母亲到孩子的证据。我们假设在抗生素治疗后，发育中的微生物组表现出韧性。在研究了这个问题之后，我们将继续检验以下特定假设：发育中的微生物组对抗生素暴露的反应部分取决于婴儿的分娩方式。我们将在较大的阿莫西林治疗的婴儿队列中研究这个问题。这项研究的长期目标是了解在幼儿发展的背景下，微生物组弹性（或崩溃）的生态基础。它将为抗生素（或其他）扰动反应的预测模型奠定重要的基础，这将有助于促进健康的微生物组传播和组装。