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

在生命的头两年中的肠道病原体感染-有或没有急性腹泻-与以下因素有关： 严重的疾病，包括腹泻、肠道损伤、生长迟缓和认知缺陷。临界电流 肠道疾病研究领域的问题是为什么有些肠道感染有症状，而有些则没有症状 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， 微生物组-肠道病原体相互作用的含义尚未得到很好的理解。越来越多的数据表明， 生命早期的累积性肠道病原体感染，即使是无症状的腹泻， 慢性肠道疾病，如环境肠道功能障碍（EED），影响儿童健康。在这 在这项研究中，我们将检验肠道微生物组特征与差异性 对急性和慢性儿童健康结果的肠道病原体感染的反应， 一项以社区为基础的出生队列研究，对来自沿着城乡梯度的三个地点的360名新生儿进行了研究。 厄瓜多尔北方沿海地区。这种设置提供了一个理想的位置来检查肠道之间的相互作用 微生物组状况和肠道感染，因为我们利用我们团队工作过的人群 15年来，这是一个肠道病原体高度传播的环境，肠道微生物组具有已知的变异性 但在其他社会、行为和遗传因素上的相对相似性可能决定了宿主 对肠道感染的反应。我们将使用最先进的诊断和基因组技术来表征 肠道病原体感染和肠道微生物群落在其生命的前两年的多个时间点， 控制与分娩方式、饮食和营养状况相关的其他因素，这些因素是已知的， 与肠道疾病有关通过这种方法，我们将分离肠道微生物组对 肠道病原体感染对健康的影响。微生物组多样性的差异， 在城市和农村地区之间进行观察也提供了机会， 婴儿肠道微生物组组成和发育的决定因素。我们的具体目标（SA）旨在 提供重要的见解：SA 1）环境条件如何影响婴儿肠道发育 SA 2）婴儿肠道微生物组是否改变急性（腹泻）和 肠道病原体感染的慢性（EED和生长迟缓）结果;以及SA 3）肠道微生物组如何 从肠道病原体感染中应答和恢复。这个项目超越了肠道的发现阶段 通过同时研究肠道微生物组和健康结果， 肠道微生物组状况的功能影响。研究结果将指导环境干预措施， 制定预防和治疗方法，以改善儿童健康结果，并将提供 用于识别微生物群落中有症状和无症状感染特征的信息 内脏

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.