Necrotizing enterocolitis involves intestinal ischemia, bacterial invasion, and transmural necrosis of the bowel wall. The immature intestinal barrier has increased permeability, reduced secretory IgA, fewer Paneth cells (which produce antimicrobial peptides), and an immature toll-like receptor 4 (TLR4) signaling system that overreacts to bacterial colonization. Hypoxic-ischemic events cause mucosal injury, allowing bacterial translocation across the gut wall. Bacteria produce hydrogen gas (pneumatosis intestinalis), which can dissect into the portal venous system (portal venous gas). Progressive necrosis leads to perforation, peritonitis, and septic shock. Human breast milk contains protective factors including IgA, lactoferrin, oligosaccharides, and growth factors that significantly reduce NEC risk.