Breast Milk Microbiota Influence on Infant Immunity and Growth (BEAMING)

摘要 了解微生物的变化以及它们如何影响疫苗反应是这项研究的核心。我们将 确定高浓缩铀婴儿中与母乳喂养相关的肠道微生物群落是否遵循相同的 作为HU控制和解决功能层面差异的继任轨迹。如何持续 来自母乳的微生物群对婴儿肠道的调节影响婴儿微生物群， 儿童疫苗接种的后续免疫应答尚不清楚，也将在本研究中进行研究。 成绩.梳理出由于HLA相关性而导致的可能的体液疫苗差异， 在确定微生物生态系统的机制和影响时要考虑的重要组成部分 通过母乳调节对疫苗的反应性。我们的意见书建议使用 在12个月的时间里，从多个地点的油井研究中定期收集生物样品， 来自尼日利亚和南非的高浓缩铀和高浓缩铀对照的母亲：婴儿对的特征队列， 研究非洲婴儿免疫力改变的宿主和微生物遗传决定因素， 因此响应RFA RM 16 -013。 我们正在进行的加拿大卫生研究所资助的队列已经招募了500多对母婴， 尼日利亚和南非母乳喂养婴儿的高浓缩铀或高浓缩铀研究先天因素和激活在艾滋病毒中的作用 感染这使我们有机会研究微生物的变化以及它们如何影响生长， 高浓缩铀婴儿对儿科疫苗的免疫应答与匹配的高浓缩铀对照相比。为此 提交，我们假设新生儿的母乳微生物群调节影响 在遗传性HLA变异体的背景下，对儿科疫苗的生长和免疫应答。 我们将通过以下具体目标来检验这一假设： 目的1：比较母乳和粪便中微生物结构和代谢物组的个体发育 相应的200个纯母乳喂养的高浓缩铀样本与100个纯母乳喂养的高浓缩铀对照样本， 出生后前12个月，记录乳汁微生物群对婴儿肠道微生物群的影响; 集体效应或与增长的联系。 目的2：评估婴儿微生物结构与小儿体液免疫应答之间的关系 疫苗 目的3：将遗传性HLA基因变异与儿童疫苗的体液免疫应答联系起来， 两个婴儿组。 该提案将探讨高浓缩铀免疫力改变的宿主和微生物遗传决定因素， 因此对RFA RM 16 -013的响应性很高。

ABSTRACT Understanding microbial shifts and how they affect vaccine response is central to this study. We will determine if gut microbial communities associated with breastfeeding in the HEU infant follows the same successional trajectory as HU controls and resolve the differences at functional level. How the continuous conditioning of the infant gut by the microbiota from the breast milk affects the infant microbiome and subsequent immune responses to pediatric vaccination is not known and would also be studied in this submission. Teasing out possible humoral vaccine differences due to HLA associations will be an important component to consider when identifying the mechanism and impact of microbial ecological conditioning through the breast milk towards vaccine responsiveness. Our submission proposes to use biological samples collected at regular intervals over a 12 month period from a multi-site study of well characterized cohort of mother: infant pairs of HEU and HU controls from Nigeria and South Africa to investigate both host and microbial genetic determinants of altered immunity in African infants and is therefore responsive to the RFA RM16-013. Our ongoing Canadian Institute of Health Research-funded cohort has enrolled over 500 mother: infant pairs of HEU or HU breastfed infants in Nigeria and South Africa to study the role of innate factors and activation in HIV infection. This has afforded us the opportunity to investigate microbial shifts and how they affect growth and immune response to pediatric vaccines in HEU infants as compared to matched HU controls. For this submission, we hypothesize that breast milk microbiota conditioning in newborn infants impacts growth and immune responsiveness to pediatric vaccines in the context of inherited HLA variants. We will test this hypothesis through the following specific aims: Aim 1: Compare the ontogeny of microbial structure and metabolome in longitudinal breast milk and stool samples of corresponding 200 Exclusively Breast Fed (EBF) HEU versus 100 EBF HU control, infants over the first 12 months of life to document influence of the milk microbiota on the infant gut microbiome; and their collective effect or association with growth. Aim 2: Assess the relationship between infant microbial structure and humoral immune responses to pediatric vaccines AIM 3: To associate inherited HLA gene variants with humoral immune responses to pediatric vaccines in the two infant groups. This proposal will interrogate both host and microbial genetic determinants of altered immunity in HEU and is therefore highly responsive to the RFA RM16-013.