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: 10541904
• 负责人: Joseph N. S. Eisenberg
• 金额: $ 103.06万
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10541904
• 关键词: Acute; Acute Diarrhea; Affect; Animals; Antibiotics; Area; Behavioral; 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; Genetic; 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; Productivity; Race; Research; Role; Rural; Sanitation; Site; Systems Development; Techniques; Testing; Therapeutic; Time; Water; Work; acute infection; acute symptom; associated symptom; 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; nutrition; pathogen; response; social; study population; therapy design; 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.

生命头两年的肠道病原体感染（无论有或没有急性症状）都与 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一个问题是，为什么有些肠道感染是有症状的，而有些则是无症状的？ 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，但是 微生物组与肠道病原体相互作用的影响尚不清楚。越来越多的数据表明 生命早期累积的肠道病原体感染，即使没有腹泻症状，也与 患有影响儿童健康的慢性肠道疾病，例如环境肠道功能障碍 (EED)。在这个 研究中，我们将检验肠道微生物组特征与差异相关的假设 通过开展一项针对急性和慢性儿童健康结果的肠道病原体感染应对措施 基于社区的出生队列研究，对来自城乡梯度三个地点的 360 名新生儿进行了研究 厄瓜多尔北部沿海。此设置提供了检查肠道之间相互作用的理想位置 微生物组状况和肠道感染，因为我们利用了我们团队工作过的人群 15 年来，这是一个高肠道病原体传播环境，肠道微生物组存在已知的变异性 其他可能决定宿主的社会、行为和遗传因素的特征和相对相似性 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 生命头两年多个时间点的肠道病原体感染和肠道微生物群落， 控制与分娩方式、饮食和营养状况相关的其他已知因素 与肠道状况有关。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。我们之前发现的微生物组多样性的差异 在城市和农村地点之间进行观察也提供了检查环境的机会 婴儿肠道微生物组成和发育的决定因素。我们设计了具体目标 (SA) 提供以下方面的重要见解：SA1) 环境条件如何影响婴儿肠道的发育 微生物组和病原体组； SA2）婴儿肠道微生物组是否会改变急性（腹泻）和 肠道病原体感染的慢性（EED 和生长迟缓）结果；和 SA3) 肠道微生物组如何 对肠道病原体感染做出反应并恢复。该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来深入了解微生物组研究 肠道微生物组条件的功能影响。结果将指导环境干预措施和 制定预防和治疗方法以改善儿童健康结果，并将提供 识别微生物群落中有症状和无症状感染特征的信息 肠道。

项目成果

Population genomics of diarrheagenic Escherichia coli uncovers high connectivity between urban and rural communities in Ecuador.

• DOI: 10.1016/j.meegid.2023.105476
• 发表时间: 2023-09
• 期刊: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases
• 作者: Rothstein AP;Jesser KJ;Feistel DJ;Konstantinidis KT;Trueba G;Levy K
• 通讯作者: Levy K

Gut Microbiome Changes with Acute Diarrheal Disease in Urban Versus Rural Settings in Northern Ecuador.

厄瓜多尔北部城市与农村地区急性腹泻病引起的肠道微生物组变化。

• DOI: 10.4269/ajtmh.20-0831
• 发表时间: 2021
• 期刊: The American journal of tropical medicine and hygiene
• 作者: Soto-Girón,MariaJ;Peña-Gonzalez,Angela;Hatt,JanetK;Montero,Lorena;Páez,Maritza;Ortega,Estefania;Smith,Shanon;Cevallos,William;Trueba,Gabriel;Konstantinidis,KonstantinosT;Levy,Karen
• 通讯作者: Levy,Karen

A Qualitative Study of Food Choice in Urban Coastal Esmeraldas, Ecuador.

• DOI: 10.1016/j.cdnut.2023.100093
• 发表时间: 2023-05
• 期刊: CURRENT DEVELOPMENTS IN NUTRITION
• 影响因子: 4.8
• 作者: Uruchima, Jessica;Renehan, Cala;Castro, Nancy;Cevallos, William;Levy, Karen;Eisenberg, Joseph Ns;Lee, Gwenyth O
• 通讯作者: Lee, Gwenyth O

Locals get travellers' diarrhoea too: risk factors for diarrhoeal illness and pathogenic Escherichia coli infection across an urban-rural gradient in Ecuador.

当地人也会患上旅行者腹泻：厄瓜多尔城乡梯度地区腹泻病和致病性大肠杆菌感染的危险因素。

• DOI: 10.1111/tmi.13183
• 发表时间: 2019
• 期刊: Tropical medicine & international health : TM & IH
• 作者: Smith,ShanonM;Montero,Lorena;Paez,Maritza;Ortega,Estefania;Hall,Eric;Bohnert,Kate;Sanchez,Xavier;Puebla,Edison;Endara,Pablo;Cevallos,William;Trueba,Gabriel;Levy,Karen
• 通讯作者: Levy,Karen

Household coping strategies associated with unreliable water supplies and diarrhea in Ecuador, an upper-middle-income country.

中高收入国家厄瓜多尔与供水不可靠和腹泻相关的家庭应对策略。

• DOI: 10.1016/j.watres.2019.115269
• 发表时间: 2020
• 期刊: Water research
• 影响因子: 12.8
• 作者: Lee,GwenythO;Whitney,HollyJ;Blum,AnnaliseG;Lybik,Noah;Cevallos,William;Trueba,Gabriel;Levy,Karen;Eisenberg,JosephNS
• 通讯作者: Eisenberg,JosephNS