Trial of Human Milk Oligosaccharide-based synbiotics for HIV-exposed uninfected children

基于母乳寡糖的合生元对暴露于艾滋病毒的未感染儿童的试验

• 批准号: 10253466
• 负责人: Rupak Shivakoti
• 金额: $ 70.08万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10253466
• 关键词: Address; Africa South of the Sahara; Age; Area; Biological; Biological Factors; Breast Feeding; Breastfed infant; Child; Clinical; Counseling; Fermentation; Growth; HIV; HIV Infections; HIV-exposed uninfected infant; Health; High Prevalence; Human Milk; Infant; Inflammation; Inflammatory; Intervention; Intervention Trial; Lead; Mediating; Metabolic Pathway; Metabolism; Morbidity - disease rate; Mothers; Observational Study; Oligosaccharides; Outcome; Pathway interactions; Pharmaceutical Preparations; Placebos; Population; Prevalence; Probiotics; Randomized; Research; Risk; Rural; Sampling; South Africa; Testing; Time; Vertical Disease Transmission; Visit; Volatile Fatty Acids; Woman; adverse outcome; antiretroviral therapy; arm; base; child bearing; cohort; comparison group; experience; follow-up; gut microbiota; health disparity; high risk; improved; infant gut microbiome; infant outcome; inflammatory marker; microbiome; microbiome composition; microbiota; mortality; mortality risk; novel; optimism; pandemic disease; prevent; randomized placebo controlled trial; randomized trial; recruit; rural South Africa; social factors; socioeconomics; success; transmission process

Project Summary HIV-exposed uninfected (HEU) infants have higher rates of mortality, infectious morbidity and growth deficits compared to HIV-unexposed uninfected (HUU) infants despite the success of maternal antiretroviral therapy (ART) in reducing vertical transmission. Our group has observed that human milk oligosaccharide (HMO) composition of breastmilk, and its relationships to the infant gut microbiome maturity and composition, may account for some of the increased risks seen in HEU infants. Currently, no specific interventions have been shown to correct for disparities in health outcomes experienced by HEU infants. To address this gap, we propose a proof-of-concept, randomized, placebo-controlled trial of a synbiotic in breast-fed HEU infants. The synbiotic is composed of 2'-fucosyllactose (2'FL) HMO and B. infantis probiotic. 2'FL is associated with reductions in mortality, infectious morbidity and growth deficits. B. infantis is included to support 2'FL fermentation and thereby maximize benefits from the 2'FL intervention. We will randomize 120 breast-fed HEU infants at 4 weeks of age 1:1 to receive synbiotic or placebo through 24 weeks of age, with a follow-up through 48 weeks of age. We will also recruit 60 breast-fed HUU infants as a comparator group and they will be followed for the same duration with no intervention. This study will be conducted in rural South Africa, in a region with high maternal HIV prevalence and high rates of infectious morbidity and growth deficits in infants. In specific aim 1, we will evaluate whether the synbiotic i) reduces infectious morbidity and growth faltering, and ii) influences biological pathways related to infant gut microbiome, metabolism, and inflammation while the intervention is in place during the first 24 weeks of age. In specific aim 2, we will evaluate whether effects persist after the intervention is discontinued through 48 weeks of age. Specific aim 3 will compare HEU and HUU cohorts and investigate biological pathways associated with infectious morbidity and growth. Overall, we hypothesize that the synbiotic will reduce infectious morbidity and improve growth in HEU infants. Our study will provide novel information on whether some of the excess risks in HEU infants can be ameliorated through interventions targeting breastfeeding-mediated microbiome and inflammatory pathways.

项目摘要 暴露于艾滋病毒的未感染婴儿的死亡率、感染发病率和生长缺陷率较高 与未暴露于艾滋病毒的未感染（HUU）婴儿相比，尽管母亲抗逆转录病毒治疗取得了成功， (ART)减少垂直传播。我们小组观察到，人乳低聚糖（HMO） 母乳的组成及其与婴儿肠道微生物组成熟度和组成的关系， 这是高浓缩铀婴儿风险增加的部分原因。目前，没有具体的干预措施， 这表明可以纠正高浓缩铀婴儿在健康结果方面的差异。为了弥补这一差距，我们 提出一个概念验证，随机，安慰剂对照试验的合生元母乳喂养的高浓缩铀婴儿。的 合生元由2 ′-岩藻糖基乳糖（2 ′ FL）HMO和B组成。益生菌。2 'FL与 降低死亡率、传染病发病率和生长缺陷。B。包括了可支持2 'FL的支架 发酵，从而最大化2 'FL干预的益处。我们将随机抽取120名母乳喂养的高浓缩铀 4周龄婴儿1：1接受合生元或安慰剂，直至24周龄，随访至 48周的年龄。我们还将招募60名母乳喂养的HUU婴儿作为对照组， 在没有干预的情况下，持续相同的时间。这项研究将在南非农村进行， 该区域孕产妇艾滋病毒感染率高，感染发病率高，婴儿发育不良。 在具体目标1中，我们将评估合生素i）是否降低感染性发病率和生长停滞， 和ii）影响与婴儿肠道微生物组、代谢和炎症相关的生物途径， 在出生后的头24周进行干预。在具体目标2中，我们将评估 在干预停止后持续到48周龄。具体目标3将比较高浓缩铀和 HUU队列研究和研究与感染发病率和生长相关的生物学途径。总的来说，我们 假设合生素将降低高浓缩铀婴儿的感染发病率并改善其生长。我们的研究 将提供新的信息，关于是否可以通过以下措施改善高浓缩铀婴儿的一些过度风险： 针对母乳喂养介导的微生物组和炎症途径的干预措施。