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

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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