Search for a command to run...
Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease predominantly affecting extremely premature infants and remains a major cause of neonatal morbidity and mortality. Increasing evidence suggests that NEC represents a spectrum of conditions driven by immaturity of intestinal immunity rather than a single disease entity. This thesis focuses on NEC associated with extreme prematurity and investigates the role of intestinal alkaline phosphatase (IAP) in its pathophysiology.<br/><br/>IAP is an apical enterocyte enzyme involved in detoxifying lipopolysaccharide (LPS) and modulating inflammatory signaling through Toll-like receptor 4 (TLR4). Using intestinal resection specimens, we demonstrated significantly reduced ileal IAP expression and enzymatic activity in NEC patients compared with controls. We also observed apical co-localization of IAP and TLR4, supporting a functional interaction relevant to intestinal inflammation. Developmental analyses of fetal ileum revealed that IAP expression emerges between 21 and 30 weeks of gestation, whereas TLR4 is expressed from early gestation onward, highlighting a developmental imbalance that may predispose the preterm gut to excessive inflammatory responses.<br/><br/>In addition, clinical analyses identified blood group AB as a significant risk factor for severe NEC and NEC related mortality, independent of fetal–maternal blood group incompatibility. <br/><br/>These findings suggest potential links between ABO blood group, IAP related pathways, and NEC severity. Together, this work identifies IAP as a key modulator of intestinal immune homeostasis in the immature gut and supports its potential as a therapeutic target for preventing or mitigating NEC in vulnerable preterm infants.