Neuroimaging and gut microbiome markers of development in HIV-exposed uninfected infants

项目摘要 非常成功的预防母婴传播（PMTCT）计划减少了 从母亲那里感染艾滋病毒的婴儿人数。2013年，有130万妇女感染艾滋病毒， 出生了199 000名感染艾滋病毒的婴儿和大约100万名接触艾滋病毒但未感染的婴儿。在 据报道，南非产前诊所的孕妇感染率为30%， 这一流行病仍然是妇女和儿童的重大公共卫生负担。母亲感染艾滋病毒可能 破坏婴儿肠道微生物组的正常发育，影响免疫系统的发育， 导致高浓缩铀婴儿发病率和死亡率较高。此外，由于微生物群的影响， 肠道和大脑之间的沟通，与母亲艾滋病毒相关的婴儿肠道微生物群的变化 感染可能有助于解释有时在高浓缩铀婴儿中观察到的神经发育延迟。 该提案建立在最近资助的一项研究的基础设施和数据之上，该研究旨在衡量 子宫内和围产期接触抗逆转录病毒疗法和艾滋病毒对发育中的婴儿大脑的影响。现有研究 跟踪210名婴儿，140高浓缩铀和70胡。在38至41周的胎龄（GA），婴儿将接受 神经成像，包括用于脑形态测量的结构成像，用于脑连接的扩散，以及 脑代谢的光谱学，以及在9和19个月大时的神经发育评估。 这项提议旨在扩大目前的研究，增加一个额外的神经影像学时间点（12 月）、婴儿肠道和母亲母乳微生物组测量和母乳低聚糖 混合物.我们将在5 - 7天、3个月和12个月时采集婴儿肠道微生物组样本。此外，乳房 将在5 - 7天和3个月时采集乳汁样本进行微生物组分析， 在前两个时间点进行低聚糖（HMO）组成分析。我们假设畸形 在高浓缩铀婴儿的神经影像学测量中发现的这些变化将与肠道微生物组多样性减少有关。的 这项研究的目的是描述婴儿大脑和肠道微生物组组成的成熟， 研究母乳HMO与微生物组组成、肠道微生物组之间的关系， 多样性和神经成像测量。我们试图确定与孕产妇艾滋病毒感染有关的差异， 深入了解高浓缩铀婴儿风险增加的情况，并揭示有针对性的干预的潜在领域， 改善健康和神经发育结果。 该项目扩展了货车德Kouwe博士（马萨诸塞州总医院）与 医院），Meintjes（开普敦大学（UCT））和劳顿（斯泰伦博斯大学），包括博士。 来自圣地亚哥大学的Lars Bode是HMO组成方面的专家，以及三个UCT 早期调查员霍姆斯卡巴和罗伯逊博士该研究旨在扩大和加强当地 能力建设和跨学科合作的重点是与当地有关的健康问题。

Project Summary Highly successful prevention of mother-to-child transmission (PMTCT) programs have reduced the number of infants acquiring HIV from their mothers. In 2013 there were 1.3 million women living with HIV who gave birth to 199,000 HIV-infected and approximately 1 million HIV-exposed, uninfected (HEU) infants. In South Africa, where a 30% infection rate is reported among pregnant women at antenatal clinics, the HIV epidemic continues to be a significant public health burden on women and children. Maternal HIV infection may disrupt normal development of the infant gut microbiome, affecting the development of the immune system and contributing to the higher morbidity and mortality of HEU infants. In addition, since microbiota influence communication between the gut and the brain, changes in the infant gut microbiota related to maternal HIV infection may help to explain the delayed neurodevelopment sometimes observed in HEU infants. This proposal builds on the infrastructure and data of a recently funded study designed to measure the effects of in utero and perinatal exposure to ART and HIV on the developing infant brain. The existing study follows 210 infants, 140 HEU and 70 HU. At 38 to 41 weeks gestational age (GA), the infants will undergo neuroimaging, including structural imaging for brain morphometry, diffusion for brain connectivity, and spectroscopy for brain metabolism, and neurodevelopmental assessments at 9 and 19 months of age. This proposal seeks to expand the current study, adding an additional neuroimaging time point (at 12 months), infant gut and maternal breast milk microbiome measures and breast milk oligosaccharide composition. We will acquire infant gut microbiome samples at 5-7 days, 3 and 12 months. In addition, breast milk samples will be acquired at 5-7 days and 3 months for microbiome analysis, and human milk oligosaccharides (HMO) composition analysis at the first two time points. We hypothesize that abnormalities identified in neuroimaging measures in HEU infants will be related to reduced gut microbiome diversity. The goals of this study are to describe the maturation of the infant brain and gut microbiome composition, and to examine the relationship between maternal breast milk HMO and microbiome composition, gut microbiome diversity and neuroimaging measures. We seek to identify differences related to maternal HIV-infection that will provide insight into increased risks of HEU infants and reveal potential areas for targeted intervention to improve health and neurodevelopmental outcomes. This project extends the existing collaboration between Drs van der Kouwe (Massachusetts General Hospital), Meintjes (University of Cape Town (UCT)) and Laughton (Stellenbosch University), to include Dr. Lars Bode from University of San Diego who is an expert in HMO composition, as well as three UCT-based early stage investigators, Drs Holmes, Kaba and Robertson. The study aims to expand and strengthen local capacity and interdisciplinary collaboration focused on locally relevant health problems.