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

项目总结/摘要 在撒哈拉以南非洲，扩大抗逆转录病毒预防措施， 预防艾滋病毒母婴传播，以及提高对 通过母乳喂养传播的风险因素，大大减少了 感染艾滋病毒的婴儿人数， 出生的未感染艾滋病毒的儿童人数上升， 感染艾滋病毒的儿童。越来越多的数据表明，这些艾滋病毒- 欧盟面临早期生命发育异常的风险，包括生长迟缓， 发病率，并增加婴儿腹泻的风险，在生命的头两年 与未感染艾滋病毒的母亲（艾滋病毒未暴露，HIV-UU）所生的儿童相比。我们 假设婴儿的肠道微生物群改变：1）遗传自母亲; 2） 在发育的关键早期持续存在; 3）有助于报告的 婴儿的生长异常和不良临床结果。调查 由马里兰州大学医学院人类研究所领导的团队 病毒学和基因组科学研究所提出微生物组影响的风险， 尼日利亚（MARGIN）研究中暴露于HIV但未感染的婴儿的生长。保证金 在增长和健康的关键时间窗口解决科学知识差距 通过这些创新的具体目标，将HIV-EU与HIV-UU进行比较： 婴儿早期肠道菌群与母体模式的关系;（2）表征 HIV-EU和HIV-UU之间婴儿肠道微生物群的功能差异 婴儿;（3）确定临床结果与结构之间的关联， 婴儿肠道菌群的功能。这种创新的战略，了解 微生物组在生长和发育中的作用不仅对 应对影响到15%新生儿的重大公共卫生挑战， 撒哈拉以南非洲，但也提供了基本的生物学洞察界面 宿主和微生物群之间的关系以及母亲在婴儿进化中的作用 微生物群从翻译的角度，本文的研究为 开发科学驱动的干预措施，如益生菌，以恢复良好的肠道 微生物群及其完整性，支持生长，并减轻持续性腹泻和其他 艾滋病毒感染者中的复发性感染-欧盟。

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.