The influence of the milk microbiome on inflammation of the preterm infant

摘要/项目摘要 早产是全世界儿科发病率和死亡率的主要原因，对健康造成灾难性影响。 结果和重大的经济影响。尽管存活率不断提高，但早产儿仍在继续 与足月出生的婴儿相比，他们遭受的结果并不理想。一种常见的 与限制早产儿生命的健康结局相关的基础是未成熟免疫- 监管和夸大的炎症反应。早产儿的肠道和大脑尤其 易受炎症影响，多项研究表明，较高水平的 在出生后的前四周，尿液和血液中就可以检测到炎性蛋白 与短期和长期的肠道和神经健康有关。母亲母乳(MBM)是 已知在婴儿期具有免疫保护性。然而，人们对新发现的牛奶知之甚少 早产后的微生物群，以及这可能对肠道或其他指标的直接影响 全身炎症。在这项研究中，我们将检验我们的总体假设，即组成群落的类群 乳汁微生物群结构对早产儿肠道和全身炎症指标的影响 新生儿早期阶段的婴儿。我们将收集早产儿的MBM、婴儿尿液和血液样本 母婴配对在四个研究时间点(1、2、4周龄和36周龄调整胎龄)。 16S rRNA测序将定义牛奶微生物组的群落结构。全基因组测序 将确定物种水平的分类群和婴儿的细菌功能潜力(基因和代谢途径) 谁有最高和最低的炎症指标，通过炎症蛋白水平来评估 包括尿肠脂肪酸结合蛋白、血清C反应蛋白、白介素1β、白介素6、白介素8、细胞间黏附分子-1。 在早产儿肠道和全身炎症的背景下定义乳汁微生物组 长期易受免疫功能损害相关的疾病将建立科学的 为寻求从治疗上丰富婴儿肠道营养来源的新型干预措施奠定基础。这些 干预措施将有可能减轻早产儿的炎症反应，从而 在一生中预防疾病和残疾。

ABSTRACT/PROJECT SUMMARY Preterm birth is the leading cause of pediatric morbidity and mortality worldwide, with catastrophic health outcomes and significant economic implications. In spite of increasing survival, children born preterm continue to suffer suboptimal outcomes when compared to their full-term born counterparts. One of the common underpinnings associated with life-limiting health outcomes of the preterm infant is immature immune- regulation and an exaggerated inflammatory response. The preterm infant gut and brain are especially vulnerable to inflammation, as evidenced by multiple studies that have reproducibly shown that higher levels of inflammatory proteins measurable in the urine and blood as early as the first four weeks following birth are associated with both short and long-term intestinal and neurological health. Maternal breast milk (MBM) is known to be immuoprotective during infancy. However, little is known about the newly discovered milk microbiome following preterm birth, and the direct influence this may have on measures of intestinal or systemic inflammation. In this study, we will test our overall hypothesis that the taxa comprising the community structure of the milk microbiome influences measures of intestinal and systemic inflammation of the preterm infant during the early neonatal period. We will collect MBM, infant urine and blood samples from preterm mother-infant pairs at four study time points (1, 2, 4 weeks of age, and 36 weeks adjusted gestational age). 16s rRNA sequencing will define the community structure of the milk microbiome. Whole genome sequencing will identify species level taxa and bacterial functional potentials (genes and metabolic pathways) in infants who have the highest and lowest measures of inflammation assessed by levels of inflammatory proteins including urinary intestinal fatty acid binding protein (iFABP), and serum-based CRP, IL1β, IL6, IL8, ICAM-1. Defining the milk microbiome in the context of intestinal and systemic inflammation among preterm infants who are vulnerable to long-term impairment associated with immune regulated disease will build the scientific foundation for novel interventions that seek to therapeutically enrich enteral sources of infant nutrition. These interventions will have the potential to attenuate the inflammatory response of the preterm infant, thereby preventing disease and disability across the lifespan.