Gut microbiome, enteric infections and child growth across a rurual urban gradient

农村城市梯度中的肠道微生物组、肠道感染和儿童生长

• 批准号: 10432022
• 负责人: Joseph N. S. Eisenberg
• 金额: $ 134.82万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-24 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10432022
• 关键词: Acute; Acute Diarrhea; Affect; Animals; Antibiotics; Area; Behavioral Genetics; Birth; Characteristics; Child; Child Health; Chronic; Cognitive deficits; Cohort Studies; Communities; Complement; Data; Development; Diagnostic; Diarrhea; Diet; Disease; Ecuador; Enteral; Environmental Exposure; Epidemiology; Functional disorder; Genomics; Growth; Health; Household; Human; Hygiene; Immune response; Immune system; Immunology; Impairment; Incidence; Individual; Infant; Infant Development; Infection; Laboratories; Latin America; Lead; Life; Location; Metagenomics; Morbidity - disease rate; Newborn Infant; Nutritional status; Outcome; Pattern; Phase; Play; Population; Population Heterogeneity; Race; Research; Role; Rural; Sanitation; Site; Systems Development; Techniques; Testing; Therapeutic; Time; Water; Work; acute infection; acute symptom; associated symptom; base; design; enteric infection; enteric pathogen; environmental intervention; experience; feeding; gut health; gut microbiome; gut microbiota; improved; infant gut microbiome; insight; interest; microbial; microbiome; microbiome composition; microbiome signature; nutrition; pathogen; response; social; study population; therapy design; therapy development; transmission process

Enteropathogen infections in the first two years of life—with or without acute symptoms—are associated with serious morbidities, including diarrhea, gut impairment, growth faltering, and cognitive deficits. A critical current question in the field of enteric diseases research is why some enteric infections are symptomatic and some are asymptomatic. Characteristics of the infant gut microbiome may influence the course of enteric infections, but the implications of microbiome-enteropathogen interactions are not well understood. Increasing data suggests that cumulative enteropathogen infections early in life, even when asymptomatic for diarrhea, are associated with chronic gut conditions, such as environmental enteric dysfunction (EED), that influence child health. In this study, we will test the hypothesis that gut microbiome characteristics are associated with differential responses to enteropathogen infections for acute and chronic child health outcomes by carrying out a community-based birth cohort study of 360 newborn infants from three sites along a rural-urban gradient in northern coastal Ecuador. This setting provides an ideal location to examine interactions between the gut microbiome conditions and enteric infections, because we leverage a population where our team has worked for 15 years that is a high enteric pathogen transmission setting with known variability in gut microbiome characteristics yet relative similarity in other social, behavioral and genetic factors that might determine host response to enteric infections. We will use state-of the-art diagnostic and genomic techniques to characterize enteropathogen infections and gut microbial communities at multiple time points over their first two years of life, controlling for other factors related to delivery mode, diet, and nutritional status that are known to be associated with gut conditions. Through this approach, we will isolate the effects of the gut microbiome on the health impacts of enteropathogen infection. The differences in microbiome diversity that we have previously observed between urban and rural sites also provides the opportunity to examine the environmental determinants of gut microbiome composition and development in infants. Our specific aims (SAs) are designed to provide important insights into: SA1) how environmental conditions affect the developing infant gut microbiome and pathobiome; SA2) whether the infant gut microbiome modifies the acute (diarrhea) and chronic (EED and growth faltering) outcomes of enteric pathogen infection; and SA3) how the gut microbiome responds and recovers from enteric pathogen infection. This project moves beyond the discovery phase of gut microbiome studies by concurrently studying gut microbiome and health outcomes to gain insights into functional implications of gut microbiome conditions. The results will guide environmental interventions and development of preventative and therapeutic approaches to improve child health outcomes, and will provide information to identify the signatures of symptomatic and asymptomatic infections in microbial communities of the gut.

在生命的头两年（随着急性症状或没有急性症状），肠病的感染与 严重的病态，包括腹泻，肠道损害，伪造和认知缺陷。关键电流 肠道疾病研究领域的问题是为什么某些肠道感染是有症状的，有些是有症状的 无症状。婴儿肠道微生物组的特征可能会影响肠道感染的过程，但 微生物组 - 肠病相互作用的含义尚不清楚。越来越多的数据表明 即使腹泻不对称的累积性肠病感染也是如此 在慢性肠道条件下，例如环保肠功能障碍（EED），会影响儿童健康。在这个 研究，我们将测试肠道微生物组特征与差异相关的假设 对急性和慢性儿童健康结果的肠病感染的反应 基于社区的出生队列研究，对来自三个地点的360名新生婴儿沿着粗糙城市的梯度进行 北部厄瓜多尔。此设置提供了检查肠道之间相互作用的理想位置 微生物组的条件和促进者，因为我们利用团队工作的人口 15年来，这是一个高促进病原体传播设置，肠道微生物组已知可变性 特征但可能决定宿主的其他社会，行为和遗传因素的相对相似性 促进感染的反应。我们将使用最先进的诊断和基因组技术来表征 在生命的头两年，肠病的感染和肠道微生物群落在多个时间点， 控制与交货模式，饮食和营养状况有关的其他因素 与肠道条件相关。通过这种方法，我们将隔离肠道微生物组对 肠病感染的健康影响。我们以前拥有的微生物组多样性的差异 在城市和粗糙的遗址之间观察到的也提供了检查环境的机会 肠道微生物组组成和婴儿发育的决定因素。我们的具体目标（SAS）是设计的 提供重要的见解：SA1）环境条件如何影响发育中的婴儿肠道 微生物组和病原体； SA2）婴儿肠道微生物组是否修饰急性（腹泻）和 肠道病原体感染的慢性（EED和生长伪造）结局； SA3）肠道微生物组如何 从肠道病原体感染中反应并恢复。该项目超越了肠道发现阶段 微生物组研究通过同时研究肠道微生物组和健康结果，以了解 肠道微生物组条件的功能意义。结果将指导环境干预措施和 开发预防和治疗方法以改善儿童健康结果，并将提供 信息以识别微生物群落中症状和不对称感染的特征 肠道。