Vitamins as modulators of neonatal intestinal injury.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal disease that primarily affects premature infants. It is characterized by intestinal injury and tissue necrosis involving both small and large intestines. Loss of epithelial barrier integrity allows enteric bacteria to translocate into the bloodstream, frequently leading to severe sepsis and high mortality, with reported rates ranging from 15 to 45%. Infants who survive often experience long-term complications, including neurodevelopmental impairment, growth restriction, and short-bowel syndrome. Vitamins help maintain intestinal barrier integrity and regulate immune and inflammatory responses, suggesting an important role in the development and progression of NEC. Vitamins are important modulators of NEC pathophysiology and may serve as adjunctive therapeutic agents through multiple molecular mechanisms. Vitamins A and D promote epithelial barrier maturation and immune homeostasis by limiting excessive Toll-like receptor 4 (TLR4) activation, a major contributor to epithelial injury and inflammation in the immature intestine. Vitamins E and C reduce oxidative stress, a key feature of NEC, while supporting regulatory T-cell function and IgA-mediated mucosal immunity. However, their use in preterm infants requires careful consideration of dosage and route of administration. Vitamin K contributes to both immune regulation and hemostasis by maintaining protein S-dependent anticoagulant activity and suppressing TLR-mediated inflammatory signaling, thereby reducing intestinal microvascular injury. Folate attenuates lipopolysaccharide-induced inflammatory responses and may strengthen host defenses against Gram-negative bacterial stimuli implicated in NEC pathogenesis. Collectively, these vitamins target key pathways involved in NEC, including TLR4 signaling, oxidative stress, epithelial barrier dysfunction, and dysregulated mucosal immunity. These findings highlight their potential roles in the prevention and attenuation of NEC. Future therapeutic strategies should focus on appropriate dosing, developmental considerations, and combination approaches to maximize efficacy while minimizing risk in preterm infants.