Early life antibiotics, gut microbiome development, and risk of childhood obesity

生命早期抗生素、肠道微生物组发育和儿童肥胖风险

基本信息

批准号：
9220708
负责人：
Jeffrey Stephen Gerber
金额：
$ 73.35万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-15 至 2021-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9220708
关键词：
Accident and Emergency department Address Adverse effects Affect Age Age-Months Animal Model Animals Antibiotic Resistance Antibiotics Asthma Biodiversity Bioinformatics Birth Birthing Centers Characteristics Child Child Care Child health care Childhood Clinical Clinical Informatics Collection Communicable Diseases Data Development Disease Electronic Health Record Enrollment Environment Epidemic Epidemiology Future Gene Expression Genes Growth Health Healthcare Hospitals Human Human Microbiome Hypersensitivity Infant Knowledge Life Link Long-Term Effects Measurement Measures Medicine Metabolic Minnesota Monitor Mothers Neonatal Neonatology Newborn Infant Nurseries Obesity Outcome Patients Pediatric Hospitals Pediatrics Pennsylvania Perinatal Pharmaceutical Preparations Philadelphia Play Population Prevalence Primary Health Care Production Public Health Recruitment Activity Research Research Personnel Risk Role Site Structure Taxonomy Time Universities Uterus Volatile Fatty Acids Weight Weight Gain Woman Work age group antimicrobial cohort critical period early childhood experience feeding gut microbiome health record intrapartum member metabolomics microbiome obesity in children obesity risk pediatrician prenatal prospective public health relevance rural setting suburb

项目摘要

DESCRIPTION (provided by applicant): One third of newborn babies in the US are exposed to antibiotics and, after discharge from the nursery, antibiotics are the most common prescription medication given to young children. Moreover, a large proportion of these perinatal and infant antibiotic exposures are unnecessary. While adverse effects of antibiotics such as the development of antibiotic resistance are well described, the patient-specific effects of antibiotic use on the long-term health of children remains unclear. The forming microbiome of the human infant is highly susceptible to disruptions, and alterations in gut bacterial species in early life during a critical period of normal colonization can have long-term effects. Early life antibiotic exposures have been associated with increased risks of obesity, allergy, and asthma. However, the potential links between varied early life antibiotic exposures, alterations in microbiome function or maturation, and health outcomes generally remain unknown. To address these knowledge gaps, we will assemble and follow longitudinally a large, diverse birth cohort to determine the relationship between (1) antibiotic exposure and gut microbiome development; (2) antibiotic exposure and weight gain/adiposity; (3) and microbiome development and weight gain/adiposity. We will examine routine intrapartum, neonatal, and infant antibiotic exposures; use bacterial taxonomic marker gene sequencing, metatranscriptomics, and metabolomics to measure antibiotic-related shifts in microbiome taxonomic carriage, biodiversity, and rate of maturation of the infant gut microbiome; and perform serial anthropometric measurements to assess weight gain and adiposity over the first 24 months of life. This project leverages complementary strengths in epidemiology, pediatrics, neonatology, infectious diseases, obesity research, clinical bioinformatics, and microbiome analysis from investigators at the University of Pennsylvania, the Children's Hospital of Philadelphia (CHOP), and the University of Minnesota. Our prior work demonstrates that (1) the investigators have extensive experience with defining the epidemiology and outcomes of antimicrobial use; the study of the mother-infant dyad in the perinatal period; the collection, processing, and analysis of human gut microbiome data; and assessing and characterizing infant and early childhood growth; 2) that antibiotic use across this population is both frequent and variable-an ideal environment to evaluate the proposed hypothesis; and 3) longitudinal early life anthropometric measurements of a cohort enrolled from birth is feasible. Through CHOP we have access to a large birthing center feeding one of the largest pediatric healthcare networks in the US using a common electronic health record. This large heterogeneous cohort is one of the key strengths of our proposal, and will enable us to recruit, follow, and monitor health records of all cohort members in real time. The establishment of a large birth cohort in which the microbiome is defined and patient health information is prospectively recorded will lead to unique future opportunities to directly link changes in the structure and function of the developing microbiome with additional health outcomes.

描述（由申请人提供）：美国三分之一的新生儿接触过抗生素，从婴儿室出院后，抗生素是幼儿最常用的处方药，而且其中很大一部分是围产期和婴儿抗生素。虽然抗生素的不良反应（例如抗生素耐药性的产生）已得到充分描述，但抗生素对患者的特定影响是不必要的。使用对儿童长期健康的影响仍不清楚。人类婴儿正在形成的微生物组极易受到生命早期肠道细菌种类的破坏和改变。在正常定植的关键时期，生命早期接触抗生素可能会产生长期影响，但与肥胖、过敏和哮喘风险增加有关。为了解决这些知识差距，我们将收集并追踪一个大型、多样化的出生队列，以确定 (1) 抗生素暴露与肠道微生物组发育之间的关系；(2) 抗生素暴露与体重增加之间的关系。肥胖; (3) 微生物组发育和体重增加/肥胖我们将检查常规产时、新生儿和婴儿抗生素暴露情况；使用细菌分类标记基因测序、宏转录组学和代谢组学来测量微生物组分类学、生物多样性和代谢组学方面与抗生素相关的变化。婴儿肠道微生物组的成熟率；并进行连续人体测量，以评估生命前 24 个月的体重增加和肥胖情况。宾夕法尼亚大学、费城儿童医院 (CHOP) 和明尼苏达大学研究人员的流行病学、儿科、新生儿学、传染病、肥胖研究、临床生物信息学和微生物组分析表明，(1)研究人员在定义围产期母婴二元组的流行病学和结果方面拥有丰富的经验；数据；以及评估和描述婴儿和幼儿成长；2）该人群中抗生素的使用既频繁又变化——这是评估所提出的假设的理想环境；3）从出生起就进行的纵向早期生命人体测量是通过 CHOP，我们可以使用通用电子健康记录进入美国最大的儿科医疗保健网络之一的大型分娩中心，这是我们提案的关键优势之一，并使我们能够招募人员。、跟踪和监控所有群组的健康记录建立一个大型出生队列，对微生物组进行定义并前瞻性地记录患者健康信息，这将带来独特的未来机会，将发育中的微生物组的结构和功能的变化与额外的健康结果直接联系起来。