Exploring novel diagnostic biomarkers and therapies for necrotising enterocolitis in preterm neonates

早产儿有坏死性小肠结肠炎（NEC）的风险，这是一种严重的胃肠道疾病，是这一人群死亡的主要原因。母乳是对该疾病最具保护作用的因素，本文将首先探讨用人类强化剂替代牛源性强化剂是否会影响婴儿微生物群的发育，这与NEC发病有关。本文将在本章的基础上，利用我们对大北方新生儿生物银行的独特访问，探索一系列样本类型和技术，以确定潜在的合适的疾病生物标志物，详见以下目标。1.1.评估牛乳强化剂与人乳强化剂对早产儿微生物群和免疫系统特定成分的影响，包括尿液和粪便中的IgA和细胞因子。1.2.评估以牛为基础（对照组）和以人为基础（干预组）的母乳强化剂与早产儿肠道微生物群之间的关系。评估牛乳强化剂与人乳强化剂对早产儿粪便和尿液中IgA和SIgA水平的影响，观察其随时间的变化。通过观察其随时间的变化，确定使用牛乳强化剂和人乳强化剂的早产儿粪便中细胞因子的差异。1.4. 评估新生儿粪便和尿液中微生物群进展与新生儿免疫系统特定成分（如IgA、SIgA和细胞因子）之间的关系。评估粪便中SCFAs与肠道微生物群组成之间的关系，并探索其作为健康（对照组）与患有nec的早产儿早期预测试验的潜在作用。确定SCFAs对粪便pH值的影响，作为NEC的潜在预测试验，评估健康对照组和NEC婴儿之间的差异。比较NEC婴儿和健康对照婴儿粪便样本中的细胞因子和肠道微生物群，评估一组细胞因子随时间的变化，以评估其作为早期预测测试候选物的潜在作用。4.1评估与健康对照相比，NEC患者粪便中ba和肠道微生物群之间的关系。比较BAs的个体种类、分组、总BAs的平均变异系数（CV-TBA）和NEC诊断风险与匹配健康对照的比较，探讨其作为早期预测试验的潜力

Preterm infants are at risk of necrotising enterocolitis (NEC), a severe gastrointestinal disease that is the leading cause of death in this population. Maternal breast milk is the most protective factor against the disease and this thesis will first explore if replacing bovine derived fortifier with human fortifier impacts infants microbiome development, which is linked to NEC onset. The thesis will build on this chapter by leveraging our unique access to the Great North Neonatal Biobank to explore a range of sample types and technologies to determine potential suitable biomarkers of disease, as detailed in the aims below.Aims:1. To evaluate the impact of bovine-based versus human-based human milk fortifiers on the microbiota and specific components of the immune systems of preterm infants, including IgA and cytokines in both urine and stools.1.1. To assess the association between bovine-based (controls) and human-based (intervention) human milk fortifiers and the gut microbiota in preterm infants.1.2. To assess the impact of bovine-based versus human-based human milk fortifiers on the levels of IgA and SIgA in stools and urine, observing its progression over time in preterm babies.1.3. To determine the differences in cytokines in stools between preterm babies fortified with bovine-based and human-based human milk fortifiers, observing its progression over time. 1.4. To evaluate associations between microbiota progression and specific components of the neonatal immune system such as IgA, SIgA and cytokines, in stool and urine.2. To evaluate the association between SCFAs in stools and gut microbiota composition and explore their potential role as an early predictor test in healthy (controls) versus preterm neonates with NEC.2.1. To determine the impact of SCFAs on stool pH as a potential predictor test for NEC, assessing the differences between healthy controls and infants with NEC.3. To compare cytokines and gut microbiota in stool samples between infants with NEC and healthy controls, evaluating changes over time of a selected panel of cytokines to assess their potential role as candidates for an early predictor test.4. To assess the association between BAs in stool and gut microbiota in the context of NEC compared to healthy controls.4.1. To compare individual species of BAs, grouped BAs, and the mean coefficient of variation of total BAs(CV-TBA) and the risk of NEC diagnosis compared to matched healthy controls, exploring their potential as an early predictor test