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

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可能导致的体液疫苗差异将是一个重要的 确定微生物生态调节的机制和影响时要考虑的组成部分 通过母乳对疫苗的反应性。我们的意见书建议使用生物 在12个月的时间里定期收集样本，这些样本来自于一项具有良好特征的多地点研究 母亲队列：来自尼日利亚和南非的一对HEU和Hu对照婴儿调查两个宿主 以及非洲婴儿免疫力改变的微生物遗传决定因素。然而，新冠肺炎大流行 然而，2021年的那次袭击使我们的工作中断了大约18个月，因为实验室被关闭了 封锁除了实验室耗材和试剂成本上涨带来的挑战外，延迟和 取消发货，以及因新冠肺炎导致工作人员和家属健康不佳而损失工时。 我们的行政补充文件要求从2023年7月1日延长至6月30日 2023年继续调查微生物的变化及其如何影响儿童的生长和免疫反应 HEU婴儿的疫苗与匹配的HU对照组的比较。我们的假设是母乳微生物区系 新生儿的条件反射影响生长和对儿科疫苗的免疫应答 遗传的人类白细胞抗原变异的背景。 我们将继续通过相同的具体目标来检验我们的假设： 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，RFA RM16-013具有很高的相关性和响应性。

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. However, the COVID-19 pandemic that hit in 2021 however disrupted our work for about 18 months since the laboratories were closed under lockdown in addition to challenges due to hike in cost of laboratory consumables and reagents, delay and cancellation of shipments, and loss of man hours due to ill health of staff and family members due to COVID-19. Our administrative supplemental submission is to request for an extension from 1 July 2023 to 30 June 2023 to continue to investigate microbial shifts and how they affect growth and immune response to pediatric vaccines in HEU infants as compared to matched HU controls. Our hypothesis is 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 continue to test our hypothesis through the same 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 relevant and responsive to the original RFA RM16-013.