Biofluid proteome profiling of perinatal infectious diseases in preterm neonates
PhD student: Tik Muk, e-mail: firstname.lastname@example.org
Department of Veterinary and Animal Sciences,
Comparative Pediatrics and Nutrition
Thesis defended: February 2020
Perinatal infectious diseases, such as chorioamnionitis (CA) and neonatal sepsis, remain a major cause of neonatal morbidity and mortality, especially for the preterm infant population. Due to their immaturity, preterm infants who are exposed to infection during the perinatal period are prone to several complications and organ injuries, such as those to the brain, gut, lung, and kidneys, in both prenatal and postnatal life. Thus, a better understanding of the underlying mechanisms and early diagnosis are important for effective prevention and treatment. However, only a few early markers of systemic and neuroinflammatory responses in neonates are known, and the underlying mechanisms remain unclear.
Purpose of the project
Using preterm pigs as a model for preterm infants, we investigated the plasma and/or cerebrospinal fluid (CSF) proteome profiling changes in response to prenatal infection, postnatal infection and antibiotics treatment to better understand how the immature organs respond to infections and to find potential early phase markers.
In SP1, the prenatal endotoxin exposure induced immune activation and potential kidney damage, partly explaining the high incidence of acute kidney injury (AKI) in preterm infants. In the foetus, the immaturity of mucosal surfaces (e.g., lungs, gut, and skin) may allow the translocation of inflammatory signals to affect more distant internal organs, e.g., the kidneys, both at birth and later. In SP2, systemic infection with Gram-positive SE induced inflammation with rapid proteome changes in plasma and CSF in preterm newborn pigs. The observed early markers of sepsis and neuroinflammation in preterm pigs may serve as novel diagnostic markers for sepsis in preterm infants. In SP3, treatment with antibiotics, regardless of the administration route, had a limited effect on systemic parameters. The observed early markers associated with NEC may serve as novel diagnostic markers for NEC, with a few of them even possessing the potential to differentiate neonatal sepsis and NEC.
Perinatal infection or inflammation induced clear signs of foetal and neonatal organ injuries and acute phase response, which lead to tremendous changes in proteome profiles in plasma and CSF. Early enteral bioactive diet feeding notably dampened changes to the plasma proteome but showed a limited effect on the CSF proteome. Several plasma proteins demonstrated early response processing, which may serve as an early indicator of neonatal infection. In addition, proteomics analysis is a promising strategy to employ as advanced technology to discover the mechanisms and potential organ injuries related to neonatal infectious diseases.