Effects of Human Milk Oligosaccharides and Gut Microbiome on Growth and Morbidity in HIV-Exposed Uninfected Infants

项目总结/摘要 尽管全球预防艾滋病毒母婴传播的卫生工作取得了成功， 和经常被忽视的艾滋病毒暴露的未感染人口， 蹒跚，感染性发病率和死亡率比HIV未暴露未感染（HUU）的婴儿。的机制 导致高浓缩铀婴儿生长不良和易受感染的原因尚不清楚，但最近的证据表明， 暗示婴儿肠道微生物组的扰动是一个关键机制。母乳在婴儿肠道中播种 微生物群落，占细菌群落的近三分之一。母乳的第三大成分 人乳低聚糖（Human milk oligosaccharides，HMO）HMO作为益生元，支持肠道生长 细菌和影响免疫系统的发展。因此，母乳含有益生元（HMO）， 益生菌（细菌）是婴儿肠道微生物组定植和发育的基础。知之甚少 关于特定的HMO和特定的肠道细菌之间的关系，可能与生长有关 和发病率。新出现的证据表明，母亲艾滋病毒感染改变了HMO的组成 高浓缩铀婴儿的微生物多样性低于高浓缩铀婴儿。考虑到健康维护组织对 微生物组发育和免疫功能，即使是HMO组成的微小差异也可能 对高浓缩铀婴儿的生长和健康结果具有重要意义。HMO可能是一种可行的干预措施， 改善高浓缩铀婴儿生长和发病率。拟议的研究将评估 母亲HIV感染，HMO组成和婴儿肠道微生物组，并确定HMO介导的 与高浓缩铀婴儿发病率和线性生长相关的途径。我们将前瞻性地注册并关注 肯尼亚是艾滋病毒高流行地区， 童年发育不良。该研究旨在：1）评估HMO成分和母乳的差异 随着时间的推移，艾滋病毒感染和未感染艾滋病毒的妇女之间的微生物群，2）了解母乳作为一种 合生素影响细菌群落和婴儿微生物组多样性，以及3）确定HMO是否 与高浓缩铀的线性增长和腹泻、肺炎和肠道功能障碍的发病率有关， HUU婴儿。这项纵向研究的结果将为我们了解生长机制提供信息， HMO和婴儿肠道微生物组的作用，为干预措施的设计提供关键数据， 优化非洲高浓缩铀儿童的生长和健康成果，这是一个脆弱和不断增长的人口。

PROJECT SUMMARY/ABSTRACT Despite the success in global health efforts to prevent mother-to-child transmission of HIV, there is a growing and often overlooked HIV-exposed uninfected (HEU) population with substantially higher risk of growth faltering, infectious morbidity, and mortality than HIV-unexposed uninfected (HUU) infants. The mechanisms responsible for poor growth and susceptibility to infection in HEU infants are unclear, but recent evidence implicates perturbations in the infant gut microbiome as a critical mechanism. Breast milk seeds the infant gut microbiome, contributing nearly one-third of bacterial communities. The third largest component of breast milk are human milk oligosaccharides (HMOs). HMOs serve as prebiotics, supporting growth of commensal gut bacteria and influencing development of the immune system. Thus, breast milk contains prebiotics (HMOs) and probiotics (bacteria) fundamental for colonization and development the infant gut microbiome. Little is known about the relationship between specific HMOs and specific gut bacteria that may be associated with growth and morbidity in HEU infants. Emerging evidence suggests that maternal HIV infection alters HMO composition and HEU infants have reduced microbial diversity than HUU infants. Given the influence of HMOs on microbiome development and immune function, even a small difference in HMO composition could have important implications for growth and health outcomes in HEU infants. HMOs may be a feasible intervention to improve growth and morbidity in HEU infants. The proposed study will evaluate the association between maternal HIV infection, HMO composition, and the infant gut microbiome, and identify HMO-mediated pathways associated with morbidity and linear growth in HEU infants. We will prospectively enroll and follow HIV-infected and HIV-uninfected women and their infants in Kenya, a region with high prevalence of HIV and poor childhood growth. The study aims to: 1) evaluate the differences in HMO composition and breast milk microbiota between HIV-infected and HIV-uninfected women over time, 2) understand how breast milk as a synbiotic influences bacterial communities and infant microbiome diversity, and 3) determine whether HMOs are associated with linear growth and incidence of diarrhea, pneumonia, and enteric dysfunction in HEU and HUU infants. Results from this longitudinal study will inform our understanding of mechanisms of growth and the role of HMOs and the infant gut microbiome, providing critical data for the design of interventions to optimize growth and health outcomes in HEU children in Africa, a vulnerable and growing population.