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

描述（由申请人提供）：在撒哈拉以南非洲，为防止母婴传播艾滋病毒而扩大抗逆转录病毒（ARV）预防，以及提高对通过母乳传播的风险因素的了解，大大减少了受感染婴儿的数量，导致暴露于艾滋病毒、未受感染（艾滋病毒-欧盟）的出生儿童的数量增加，甚至使感染艾滋病毒的儿童的惊人数量相形见绌。越来越多的数据表明，与未感染艾滋病毒的母亲所生的婴儿（HIV-unexposed, HIV- uu）相比，这些HIV- EU的婴儿在生命早期发育异常的风险中，包括生长迟缓、更高的发病率和在生命的头两年婴儿腹泻的风险增加。我们假设婴儿肠道菌群的改变：1)遗传自母亲；2)持续超过发育的关键早期；3)有助于报道婴儿的生长异常和不良临床结果。由马里兰大学医学院人类病毒学研究所和基因组科学研究所领导的这个调查小组提出了微生物组影响尼日利亚暴露于艾滋病毒但未感染的婴儿生长风险的研究（MARGIN）。与HIV-UU相比，MARGIN通过这些创新的具体目标解决了HIV-EU生长和健康关键时间窗口的科学知识空白：(1)表征婴儿早期肠道微生物群与母体模式的关系；(2)表征HIV-EU和HIV-UU婴儿肠道微生物群功能差异；(3)确定临床结果与婴儿肠道菌群结构和功能之间的关系。这一了解微生物群在生长发育中的作用的创新策略不仅对解决影响撒哈拉以南非洲15%新生儿的重大公共卫生挑战具有重要意义，而且还为宿主和微生物群之间的界面以及母亲在婴儿微生物群进化中的作用提供了基本的生物学见解。从转化的角度来看，本研究为开发科学驱动的干预措施（如益生菌）奠定了基础，以恢复有利的肠道微生物群及其完整性，支持生长，减轻HIV-EU患者的持续性腹泻和其他复发性感染。

DESCRIPTION (provided by applicant): 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.