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

城乡梯度的肠道微生物组、肠道感染和儿童生长

• 批准号: 9974179
• 负责人: Joseph N. S. Eisenberg
• 金额: $ 48.13万
• 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 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9974179
• 关键词: Affect; Animal Sources; Animal Testing; Animals; Area; Caregivers; Characteristics; Child; Child Development; Child Health; Cohort Studies; Communities; DNA Sequence; Data; Data Collection; Development; Diarrhea; Ecuador; Ecuadorian; Enrollment; Enteral; Environment; Environmental Microbiology; Epidemiology; Exposure to; Feces; Functional disorder; Goals; Growth; Health; Household; Human; Infant; Life; Low income; Measurement; Measures; Methods; Microbiology; Nutritional; Outcome; Outcome Measure; Parents; Pathway interactions; Phase; Play; Qualitative Methods; Reporting; Research; Risk; Role; Route; Rural; Rural Community; Shapes; Shotguns; Site; Source; Structure; Surveys; Taxonomy; Testing; Zoonoses; base; cohort; enteric infection; enteric pathogen; gut microbiome; gut microbiota; health management; indexing; infant animal; infant gut microbiome; infant outcome; innovation; insight; low and middle-income countries; metagenomic sequencing; microbial; microbiome; microbiome sequencing; microorganism; tool; training opportunity; transmission process; uptake

Animals are ubiquitous in both urban and rural communities in low- and middle-income countries, and recent evidence suggests that animal exposure is an important, yet often overlooked factor shaping infant gut health and development. While connections between animal exposure and the gut microbiome are increasingly recognized, the health impacts of these associations are unclear. The goal of this study is to understand if and how animal exposures affect gut characteristics and health outcomes of infants enrolled in an ongoing cohort study in northern Ecuador. Our proposed mixed methods approach will result in a comprehensive understanding of infant exposure to animals and animal-sourced contamination, and how this varies along an urban-rural gradient. We will collect rich and nuanced data on household and infant animal interactions and exposures from this proposal and leverage the extensive health and microbiome data being collected within our ongoing cohort study to examine the implications of exposures to animals on the infant gut microbiome and health outcomes during the first two years of life. Through this competing revision proposal we thus substantially expand the scope of our existing study to characterize a potentially key pathway for infant exposure to enteropathogens and other microorganisms. Our specific aims are: SA1) To characterize infant exposure to animals and animal feces using environmental microbiology, qualitative, and survey-based methods. We will use environmental microbiology methods to quantify and differentiate human- and animal- specific fecal contamination in study households (SA1a), and use qualitative methods to understand the conditions under which children are exposed to animals and animal-sourced contamination, and to gain insights into feasible strategies for managing health risks associated with animal exposure (SA1b). We will integrate these data to develop complementary microbial and survey-based indices of animal exposure, that will be used as exposure variables measures in subsequent analyses. SA2) To test the association between animal exposure and infant gut microbiome characteristics. We will use microbiome sequencing data generated in the parent study to examine associations between animal exposure and gut microbiome of cohort children (SA2a). We will also look for evidence of zoonotic transmission of microorganisms between infants and animals by testing for the presence of animal-specific sequences within the microbiomes of highly exposed children (SA2b). SA3) To test the association between animal exposure and infant gut health. We will use health outcome data from the parent study to examine associations between animal exposure and diarrhea, enteropathogen infections, infant growth, and environmental enteric dysfunction, adjusting for key covariates (SA3a). This project integrates additional interdisciplinary expertise into our study team (qualitative, measurement development, and microbial source tracking methods), provides substantive additional training opportunities for our Ecuadorian team, and increases the translational aspects of our research.

动物在低收入和中等收入国家的城市和农村社区中无处不在，最近 有证据表明，动物接触是影响婴儿肠道健康的一个重要但经常被忽视的因素 和发展。虽然动物暴露与肠道微生物组之间的联系越来越多 众所周知，这些关联对健康的影响尚不清楚。这项研究的目的是了解是否 以及动物暴露如何影响参加一项研究的婴儿的肠道特征和健康结果 厄瓜多尔北部正在进行的队列研究。我们提出的混合方法将导致 全面了解婴儿接触动物和动物源性污染的情况，以及如何做到这一点 沿城乡梯度变化。我们将收集有关家庭和婴儿动物的丰富而细致的数据 该提案中的相互作用和暴露，并利用广泛的健康和微生物组数据 我们正在进行的队列研究中收集了这些数据，以检查接触动物对婴儿肠道的影响 生命头两年的微生物组和健康结果。通过这个竞争性的修订提案 因此，我们大大扩展了现有研究的范围，以描述婴儿的潜在关键途径 接触肠道病原体和其他微生物。我们的具体目标是： SA1) 表征婴儿 使用环境微生物学、定性和基于调查的方法接触动物和动物粪便 方法。我们将使用环境微生物学方法来量化和区分人类和动物 研究家庭中特定的粪便污染（SA1a），并使用定性方法来了解 儿童接触动物和动物源性污染的条件，并获得 深入了解管理与动物暴露相关的健康风险的可行策略（SA1b）。我们将 整合这些数据来制定补充微生物和基于调查的动物暴露指数， 将在后续分析中用作暴露变量测量。 SA2) 测试之间的关联 动物暴露和婴儿肠道微生物组特征。我们将使用微生物组测序数据 在母研究中生成，用于检查动物暴露与队列肠道微生物组之间的关联 儿童（SA2a）。我们还将寻找婴儿之间微生物人畜共患传播的证据 和动物，通过测试高度暴露的微生物组中是否存在动物特异性序列 儿童（SA2b）。 SA3) 测试动物暴露与婴儿肠道健康之间的关联。我们将使用 来自家长研究的健康结果数据，用于检查动物暴露与腹泻之间的关联， 肠道病原体感染、婴儿生长和环境肠道功能障碍，调整关键协变量 （SA3a）。该项目将额外的跨学科专业知识整合到我们的研究团队中（定性、 测量开发和微生物源追踪方法），提供实质性的额外培训 为我们厄瓜多尔团队提供机会，并增加我们研究的转化方面。