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

母乳低聚糖和肠道微生物组对暴露于 HIV 的未感染婴儿生长和发病的影响

• 批准号: 9920737
• 负责人: Grace M Aldrovandi
• 金额: $ 70.86万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-24 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9920737
• 关键词: Africa; Bacteria; Bifidobacterium; Breast Feeding; Cattle; Child; Childhood; Clinical Research; Cross-Sectional Studies; Data; Development; Diarrhea; Enrollment; Enteral; Functional disorder; Growth; HIV; HIV Infections; HIV-exposed uninfected infant; Health; High Prevalence; Human Milk; Immune; Immune system; Incidence; Infant; Infant Development; Infection; Ingestion; Intervention; Kenya; Lactation; Longitudinal Studies; Malnutrition; Mediating; Molecular Epidemiology; Morbidity - disease rate; Mother-to-child HIV transmission; Mus; Oligosaccharides; Outcome; Pathway interactions; Pneumonia; Population; Postpartum Period; Predisposition; Prevalence; Prevention; Probiotics; Prospective Studies; Prospective cohort study; Research; Risk; Role; Seeds; Time; Variant; Woman; bacterial community; bone; cohort; dysbiosis; epidemiology study; experience; feeding; follow-up; global health; gut bacteria; gut microbiome; gut microbiota; high risk; immune function; improved; infant gut microbiome; innovation; lacto-N-neotetraose; lean body mass; microbial; microbiome; microbiota; mortality; prebiotics; prevent; programs; prospective; success; therapy design

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.

项目摘要/摘要 尽管全球卫生努力取得了成功，以防止母亲到孩子的艾滋病毒传播，但越来越多 而且经常被忽视的艾滋病毒暴露于未感染的（HEU）人口，其增长风险更高 与未暴露的未感染（HUU）婴儿相比，步履蹒跚，传染性发病率和死亡率。机制 负责HEU婴儿的增长不良和对感染的敏感性尚不清楚，但最近的证据 含义是婴儿肠道微生物组的扰动作为一种关键机制。母乳种子婴儿肠道 微生物组，贡献了近三分之一的细菌群落。母乳的第三大组成部分 是人乳寡糖（HMOS）。 HMO用作益生元，支持共生肠的增长 细菌和影响免疫系统的发展。因此，母乳含有益生元（HMO）和 益生菌（细菌）定殖和发育的基础婴儿肠道微生物组。鲜为人知 关于特定的HMO与可能与生长有关的特定肠道细菌之间的关系 和HEU婴儿的发病率。新兴的证据表明，母体艾滋病毒感染改变了HMO组成 与HUU婴儿相比，HEU婴儿的微生物多样性降低。鉴于HMO对 微生物组的发展和免疫功能，即使HMO组成的差异很小 对HEU婴儿的成长和健康成果的重要意义。 HMO可能是可行的干预措施 改善HEU婴儿的生长和发病率。拟议的研究将评估 母体HIV感染，HMO组成和婴儿肠道微生物组，并鉴定HMO介导的 与HEU婴儿的发病率和线性生长有关的途径。我们将前景注册并关注 肯尼亚的艾滋病毒感染和艾滋病毒未感染的妇女及其婴儿，一个艾滋病毒率高的地区 童年不良的成长。该研究的目的是：1）评估HMO成分和母乳的差异 随着时间的推移，艾滋病毒感染和艾滋病毒未感染的妇女之间的菌群，2）了解母乳如何 合成型影响细菌群落和婴儿微生物组的多样性，3）确定HMOS是否是否 与HEU和 胡乌婴儿。这项纵向研究的结果将为我们了解增长机制和 HMOS和婴儿肠道微生物组的作用，为设计干预措施提供关键数据 优化非洲HEU儿童的增长和健康成果，这是一个脆弱和增长的人口。