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

项目摘要/摘要 在撒哈拉以南非洲，扩大抗逆转录病毒(ARV)预防的规模 预防母婴传播艾滋病毒，以及提高对 通过母乳喂养传播的风险因素大大减少了 婴儿受到感染的人数导致接触艾滋病毒的人数， 未感染(HIV-EU)儿童的出生人数甚至超过了令人震惊的 感染艾滋病毒的儿童。被低估的是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，更高 在生命的头两年，婴儿腹泻的发病率和风险增加 与未感染艾滋病毒的母亲(艾滋病毒未暴露，艾滋病毒-解脲支原体)所生的孩子相比。我们 假设婴儿肠道微生物区系改变：1)遗传自母亲；2) 在发育的关键早期阶段持续存在；以及3)对报告的 婴儿的发育异常和不良的临床结局。调查性的 由马里兰大学医学院人类研究所领导的研究小组 病毒学和基因组科学研究所提出微生物组影响感染风险 尼日利亚暴露于艾滋病毒但未感染的婴儿的生长(边缘)研究。保证金 解决增长和健康关键时间窗口中的科学知识差距 通过这些创新的具体目标将艾滋病毒-欧盟与艾滋病毒-解脲支原体进行比较：(1)表征 婴儿早期肠道微生物区系与母体模式的关系；(2)表征 HIV-EU和HIV-UU婴儿肠道微生物区系的功能差异 婴儿；(3)确定临床结果与结构和 婴儿肠道微生物区系的功能。这一创新战略有助于理解 微生物组在生长和发育中的作用不仅对 应对重大的公共卫生挑战，影响到年内15%的新生儿 撒哈拉以南非洲，也提供了对界面的基本生物学见解 宿主和微生物区系之间的关系以及母亲在婴儿进化中的作用 微生物区系。从翻译的角度来看，这项研究为 发展科学驱动的干预措施，如益生菌，以恢复良好的肠道 微生物区系及其完整性，支持生长，缓解持续性腹泻和其他 艾滋病毒-欧盟地区的反复感染。

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.