Diana Szczepańska, Agnieszka Siwiec, Maria Morawska, Aleksander Ruszkiewicz, Alicja Ożga, Anna Dargacz, Daria Drężek, Julia Kozikowska, Klaudia Szymczyk, Maciej Jakubik, Marta Kiżewska, Marta Owczarzak, Aleksandra Gajos, Zuzanna Wójcik, Michalina Raczkowska
Research objective: The aim of this study is to summarize current evidence on the role of inflammatory mediators and intestinal dysbiosis in the pathogenesis of necrotizing enterocolitis (NEC) — one of the most serious gastrointestinal disorders of neonates and infants, occurring predominantly in preterm infants with very low birth weight (VLBW) — and to discuss the underlying molecular and immunological mechanisms. Methodology: The study is based on a review of the available scientific literature, with particular attention to the contribution of selected leukocyte populations, excessive activation of Toll-like receptors (TLRs), especially Toll-like receptor 4 (TLR-4), and alterations in the intestinal microbiota to the initiation and perpetuation of the inflammatory response associated with NEC. Main conclusions: Intestinal dysbiosis, exaggerated activation of the innate immune response, and immaturity of the neonatal immune system are key contributors to the development and progression of NEC, with dysregulated TLR-4 signaling and aberrant inflammatory responses playing central roles in intestinal injury. Despite advances in neonatal intensive care, NEC remains associated with high morbidity and mortality, particularly in patients with Bell's stage III disease. Application of the study: Early recognition of NEC, despite its frequently nonspecific clinical manifestations, together with a better understanding of its underlying pathophysiological mechanisms, may support clinicians in refining therapeutic strategies and increasing survival rates among affected neonates and infants. Originality/Novelty of the study: The review integrates current evidence on the interplay between intestinal dysbiosis and the immature neonatal innate immune system, highlighting dysregulated TLR-4 signaling as a central mechanism of intestinal injury and pointing to the microbiota as a potential target in the prevention and management of NEC.