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

探索早产儿坏死性小肠结肠炎的新型诊断生物标志物和疗法

• 批准号: 2884813
• 金额: --
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2884813
• 关键词: Exploring; novel; diagnostic; biomarkers; therapies

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

早产儿有患坏死性小肠结肠炎(NEC)的风险，这是一种严重的胃肠道疾病，是这一人群的主要死亡原因。母乳是预防NEC的最有效因素，本论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的微生物群发育，这与NEC的发病有关。本论文将在本章的基础上，利用我们对大北方新生儿生物库的独特访问，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。目的：1.评估基于牛的和基于人的母乳强化剂对早产儿免疫系统微生物区系和特定成分的影响，包括尿液和粪便中的IgA和细胞因子。评估以牛为基础的(对照)和以人为基础的(干预)母乳强化剂与早产儿肠道微生物区系之间的联系。评估以牛为基础和以人为基础的母乳强化剂对粪便和尿液中IgA和SIgA水平的影响，观察其在早产儿中随时间的进展情况。目的：确定补充牛乳和人乳强化的早产儿粪便中细胞因子的差异，观察其随时间的进展。1.4.目的：1.评估微生物区系进展与新生儿免疫系统的特定成分，如粪便和尿液中的IgA、SIgA和细胞因子之间的关系。评估粪便中单链脂肪酸与肠道微生物区系组成之间的关系，并探索其作为健康(对照)早产儿与早产儿NEC.2.1的早期预测试验的潜在作用。为了确定单链脂肪酸对粪便pH值的影响作为NEC的潜在预测试验，评估健康对照组和患有NEC.3的婴儿之间的差异。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区系，评估选定的一组细胞因子随时间的变化，以评估它们作为早期预测测试候选者的潜在作用。4.与健康对照组比较，评估NEC患者粪便中BAs与肠道微生物区系之间的关系。与匹配的健康对照组比较不同种类的bas、成组bas和总bas的平均变异系数(cv-tba)和诊断NEC的风险，探索它们作为早期预测试验的潜力。