Inflammatory stress and the compromised intestinal mucosal barrier: insights and interventions for perinatal health

Preterm children are at an increased risk of various health problems throughout their lives. An important risk factor for preterm birth is a bacterial infection of the fetal membranes (chorion and amnion) and the amniotic fluid during pregnancy, also known as chorioamnionitis. Chorioamnionitis can lead to inflammation of various organs in the baby. The inflammatory response caused by an infection can spread and affect different systems in the body, with potentially serious consequences. Chorioamnionitis can increase the risk of damage and inflammation of the intestines, which can eventually lead to necrotizing enterocolitis (NEC), a severe intestinal disease that can cause long-term digestive problems. Nearly one in three children with NEC dies from this disease, while the remaining preterm infants can only be treated symptomatically and struggle with health problems for the rest of their lives. One of the characteristics of NEC is a reduced function of the intestinal mucosal barrier. This barrier consists of various components that work together to protect the intestinal wall from harmful substances, pathogens, and inflammatory reactions. This dissertation has demonstrated that chorioamnionitis can impair this intestinal mucosal barrier even before birth, resulting in decreased functionality of this barrier. This makes preterm babies more susceptible to develop intestinal diseases after birth, including NEC. Treatment options that can be applied as early as possible and that target multiple disease mechanisms are important to maintain or improve the integrity of the intestinal barrier in vulnerable babies to reduce the risk of developing intestinal diseases, including NEC.