Microbiome Affects Risk of Growth in HIV-exposed but Unifected Infants-Nigeria

微生物组影响暴露于艾滋病毒但未感染的婴儿的生长风险 - 尼日利亚

• 批准号: 8932593
• 负责人: Manhattan E Charurat
• 金额: $ 60.04万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-23 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8932593
• 关键词: Address; Affect; Africa South of the Sahara; Age; Anti-Retroviral Agents; Antibiotics; Bacterial Translocation; Bacterial Vaginosis; Base Composition; Biological; Birth; Breast Feeding; Child; Child Development; Childhood; Clinical; Data; Development; Developmental Delay Disorders; Diarrhea; Dietary Supplementation; Evolution; Exclusive Breastfeeding; Exposure to; Feces; Food; Foundations; Genome; Growth; Growth and Development function; HIV; HIV Infections; HIV-exposed uninfected infant; Health; Human Virology; Immune system; Immunologic Deficiency Syndromes; Infant; Infantile Diarrhea; Infection; Inherited; Institutes; Intervention; Knowledge; Life; Low Birth Weight Infant; Malaria; Malnutrition; Maryland; Maternal Age; Maternal Exposure; Measures; Meconium; Metabolism; Morbidity - disease rate; Mothers; Newborn Infant; Nigeria; Outcome; Pattern; Permeability; Phylogenetic Analysis; Pneumonia; Premature Birth; Prevention; Probiotics; Property; Prophylactic treatment; Public Health; Recurrence; Reporting; Ribosomal RNA; Risk; Risk Factors; Role; Sampling; Science; Skin; Structure; Time; Universities; Vagina; Woman; feeding; gastrointestinal; gut microbiota; improved; infant outcome; innovation; insight; medical schools; microbiome; prenatal exposure; public health relevance; scale up; sugar; transmission process

Project Summary/Abstract In sub-Saharan Africa, the scale-up of antiretroviral (ARV) prophylaxis for the prevention of mother-to-child HIV transmission, as well as improved understanding of risk factors for transmission through breastfeeding, have dramatically reduced the number of infants becoming infected resulting in the number of HIV-exposed, uninfected (HIV-EU) children being born rising to dwarf even the staggering number of children infected with HIV. Under appreciated is a growing body of data that these HIV- EU are at risk for early life development abnormalities including growth faltering, higher morbidities, and increased risk for infant diarrhea during the first two years of life compared to children born to HIV-uninfected mothers (HIV-unexposed, HIV-UU). We hypothesize that the infant's altered gut microbiota: 1) is inherited from the mother; 2) persists over the critical early age of development; and 3) contributes to the reported growth abnormalities and adverse clinical outcomes for the infant. The investigative team, led by the University of Maryland School of Medicine's Institute of Human Virology and Institute for Genome Sciences proposes the Microbiome Affects Risk of Growth in HIV-exposed but Uninfected Infants in Nigeria (MARGIN) Study. MARGIN addresses scientific knowledge gaps in the critical window of time for growth and health of HIV-EU compared to HIV-UU through these innovative specific aims: (1) Characterize the relationship of infants' early gut microbiota to maternal pattern; (2) Characterize the functional differences in the infant gut microbiota between HIV-EU and HIV-UU infants; (3) Determine the associations between clinical outcomes and the structure and function of the infants' gut microbiota. This innovative strategy for understanding the role of the microbiome in growth and development not only has implications for addressing the significant public health challenge impacting 15% of all newborn babies in sub-Saharan Africa but also provides fundamental biological insight into the interface between host and microbiota and the role of the mother in the evolution of infant microbiota. From a translational perspective, this study lays the foundation for developing science-driven interventions such as probiotics to restore a favorable gut microbiota and its integrity, support growth, and mitigate persistent diarrhea and other recurrent infections among HIV-EU.

项目摘要/摘要 在撒哈拉以南非洲，抗逆转录病毒（ARV）预防的规模扩大 预防母子艾滋病毒的传播，以及对 通过母乳喂养传播的危险因素，大大降低了 被感染的婴儿数量导致艾滋病毒暴露的数量， 未感染的（HIV-eu）儿童天生就会矮小到矮人 感染艾滋病毒的儿童。不足以欣赏的是越来越多的数据体系 欧盟有早期生命发展异常的风险，包括增长步履蹒跚，更高 在生命的头两年中，病毒性和婴儿腹泻的风险增加 与艾滋病毒未感染的母亲（HIV-Unceed，HIV-UU）出生的孩子相比。我们 假设婴儿的肠道菌群改变：1）是从母亲那里遗传而来的； 2） 在临界的发展时代持续存在； 3）有助于报告 婴儿的生长异常和不良临床结果。调查 由马里兰大学医学院人类学院领导的团队 病毒学和基因组科学研究所提出微生物组会影响 尼日利亚（Margin）研究中艾滋病毒暴露但未感染的婴儿的增长。利润 在关键的时间范围内解决科学知识差距 通过这些创新的特定目的与HIV-UU相比，HIV-eu的eu：（1）表征 婴儿的早期肠道菌群与母体模式的关系； （2）表征 HIV-EU和HIV-UU之间婴儿肠道菌群的功能差异 婴儿； （3）确定临床结果与结构之间的关联和 婴儿肠道菌群的功能。这种理解的创新策略 微生物组在增长和发展中的作用不仅对 应对影响所有新生婴儿中15％的公共卫生挑战 撒哈拉以南非洲，但也提供了对界面的基本生物学见解 在宿主和微生物群之间以及母亲在婴儿演变中的作用 微生物群。从转化的角度来看，本研究为 开发以科学为导向的干预措施，例如益生菌，以恢复有利的肠道 微生物群及其完整性，支持增长和减轻持续性腹泻和其他 HIV-EU之间的复发感染。