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（由申请人证明）：三分之一的新生婴儿暴露于抗生素中，在托儿所的出院后，最常见的是给幼儿的最常见的人。虽然抗生素等抗生素耐药性的不良对抗生素的特异性作用是抗生素的特异性作用 在儿童的长期健康状态不清楚的是人类婴儿的早期细菌中的高度压力 在正常定植的关键时期，长期的Exposurec Exposurec ExposUREC是肥胖，过敏和哮喘，但是，生命寿命与微生物组功能或含量之间的潜在联系，以及健康效果知识hort确定（1）抗生素暴露与肠道微生物组的发展之间的关系；在微生物组中，生物多样性和婴儿肠道微生物组的生物多样性；宾夕法尼亚大学的调查人员，明尼苏达州的费城儿童医院（CHOP）。 ; Birthing Center是所有同类成员的最大的电子记录之一发展微生物组的功能以及其他健康结果。