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

摘要 了解微生物的变化及其如何影响疫苗反应是这项研究的核心。我们会 确定HEU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方法 HU控制和解决功能层面上的差异的演替轨迹。如何持续 来自母乳的微生物群对婴儿肠道的调节作用会影响婴儿的微生物群和 儿科疫苗的后续免疫反应尚不清楚，也将在本研究中进行研究 呈件。梳理出由于人类白细胞抗原相关性而可能出现的体液疫苗差异将是一个 确定微生物生态系统的机制和影响时需要考虑的重要因素 通过母乳调节疫苗的反应性。我们的意见书建议使用 在12个月的时间里定期从井的多个地点研究中收集生物样本 典型的母亲队列：来自尼日利亚和南非的HEU和HU婴儿对对照 调查非洲婴儿和IS免疫改变的宿主和微生物遗传决定因素 因此，响应RFA RM16-013。 我们正在进行的加拿大健康研究所资助的队列已经招募了500多对母亲：婴儿 尼日利亚和南非HEU或HU母乳喂养婴儿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及其如何影响生长和 与匹配的HU对照组相比，HEU婴儿对儿科疫苗的免疫应答。为了这个 提交，我们假设母乳微生物区系调节对新生儿的影响 遗传的人类白细胞抗原变异背景下儿童疫苗的生长和免疫反应性。 我们将通过以下具体目标来检验这一假设： 目的1：比较纵向母乳和大便中微生物结构和代谢组的个体发育 相应的200名纯母乳喂养(EBF)婴儿的HEU样本与100名EBF HU对照婴儿的样本 生命的前12个月记录乳汁微生物群对婴儿肠道微生物群的影响；以及他们的 与增长有关的集体效应或联系。 目的2：探讨婴幼儿微生物结构与体液免疫应答的关系 疫苗 目的：探讨遗传的人类白细胞抗原基因变异与儿童疫苗体液免疫应答之间的关系。 两组婴儿。 这项建议将询问宿主和微生物在HEU和IS中改变免疫的遗传决定因素 因此，对RFA RM16-013高度响应。

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.