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.

生命最初两年的肠道病原体感染（不论有无急性症状）与以下疾病有关