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

在生命的头两年--有或没有急性症状--的肠道病原体感染与 严重的疾病，包括腹泻、肠道功能障碍、发育迟缓和认知缺陷。一股临界水流 肠道疾病研究领域的问题是，为什么一些肠道感染是有症状的，而另一些是 没有任何症状。婴儿肠道微生物群的特征可能会影响肠道感染的过程，但 微生物群-肠道病原体相互作用的含义还没有被很好地理解。越来越多的数据表明 在生命早期，即使在没有腹泻症状的情况下，累积的肠道病原体感染也与 患有慢性肠道疾病，如环境肠道功能障碍(EED)，影响儿童健康。在这 研究中，我们将检验肠道微生物组特征与差异有关的假设 通过开展肠道病原体感染对急性和慢性儿童健康结局的反应 年城乡梯度3个地点360名新生儿社区出生队列研究 厄瓜多尔北部沿海地区。此设置为检查肠道之间的相互作用提供了理想的位置 微生物群条件和肠道感染，因为我们利用我们团队工作过的人群 15年来，这是一种肠道病原体高度传播的环境，肠道微生物群具有已知的变异性。 可能决定宿主的其他社会、行为和遗传因素的特征但相对相似 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头两年中的多个时间点， 控制其他与分娩方式、饮食和营养状况有关的已知因素 与肠道疾病相关的。通过这种方法，我们将分离肠道微生物群对 肠道病原体感染对健康的影响。我们以前在微生物群多样性方面的差异 城市和农村之间的观察也提供了检查环境的机会 婴儿肠道微生物群组成和发育的决定因素。我们的具体目标(SA)是设计的 为以下方面提供重要见解：1)环境条件如何影响婴儿发育的肠道 微生物群和致病菌群；SA2)婴儿肠道微生物群是否修改急性(腹泻)和 肠道病原体感染的慢性(EED和生长受阻)结局；以及SA3)肠道微生物群如何 对肠道病原体感染作出反应并康复。该项目超越了GUT的发现阶段 通过同时研究肠道微生物组和健康结果来进行微生物组研究，以获得对 肠道微生物群条件的功能含义。研究结果将指导环境干预和 制定预防和治疗方法，以改善儿童健康结果，并将提供 的微生物群落中识别有症状和无症状感染特征的信息 我的直觉。

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.