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

• 批准号: 9104595
• 负责人: Jeffrey Stephen Gerber
• 金额: $ 79.6万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 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/9104595
• 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; Lead; 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; Process; Production; Public Health; Recruitment Activity; Research; Research Personnel; Risk; Role; Rural; 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; suburb

 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。此外，这些围产期和婴儿抗生素暴露中很大一部分是不必要的。虽然抗生素的副作用（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 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 在正常定殖的关键时期可能会产生长期影响。生命早期接触抗生素与肥胖、过敏和哮喘的风险增加有关。然而，不同的生命早期抗生素暴露、微生物组功能或成熟的改变以及健康结果之间的潜在联系通常仍然未知。为了解决这些知识差距，我们将收集并纵向跟踪一个大型、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) 抗生素暴露和体重增加/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携带、生物多样性和婴儿肠道微生物组成熟率中与抗生素相关的变化；并进行一系列人体测量，以评估生命前 24 个月内的体重增加和肥胖情况。该项目利用了宾夕法尼亚大学、费城儿童医院 (CHOP) 和明尼苏达大学研究人员在流行病学、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方面的互补优势。我们之前的工作表明：(1) 研究人员在定义抗菌药物使用的流行病学和结果方面拥有丰富的经验；围产期母婴二元关系的研究；人类肠道微生物组数据的收集、处理和分析；评估和描述婴儿和幼儿成长的特征； 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) 对从出生起就登记的队列进行纵向早期生命人体测量是可行的。通过 CHOP，我们可以使用通用电子健康记录访问一家大型分娩中心，该中心为美国最大的儿科医疗保健网络之一提供服务。这个庞大的异构队列是我们提案的关键优势之一，将使我们能够实时招募、跟踪和监控所有队列成员的健康记录。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，将带来独特的未来机会，将发育中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。