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

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.梳理出可能的体液疫苗差异由于HLA协会将是一个重要的 确定微生物生态调节的机制和影响时要考虑的因素 通过母乳来提高疫苗的反应性。我们的意见书建议使用生物 在12个月的时间里，从一个多地点的研究中定期收集的样本， 来自尼日利亚和南非的母亲：婴儿高浓缩铀和高浓缩铀对照组队列，以研究两种宿主 以及非洲婴儿免疫力改变的微生物遗传决定因素。然而，2019冠状病毒病疫情 然而，2021年的袭击使我们的工作中断了约18个月，因为实验室在2018年关闭， 除了由于实验室消耗品和试剂成本上涨、延迟和 由于COVID-19导致员工及家属健康欠佳，取消付运及损失工时。 我们的行政补充申请是要求从2023年7月1日延长至6月30日 2023年继续研究微生物的变化以及它们如何影响儿童的生长和免疫反应。 高浓缩铀婴儿与高浓缩铀对照组相比，我们的假设是母乳微生物群 新生儿的调理影响儿童的生长和对儿科疫苗的免疫反应， 遗传性HLA变体的背景。 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，与原始RFA RM 16 -013高度相关并响应。

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. 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.