What is Necrotizing Enterocolitis (NEC)?

Necrotizing enterocolitis (NEC) is a serious gastrointestinal emergency primarily affecting premature infants, particularly those born before 32 weeks gestation or with very low birth weight. NEC is characterized by inflammation and necrosis (tissue death) of the intestinal mucosa, leading to bowel wall necrosis, perforation, and potentially life-threatening complications.


The exact cause of NEC is not fully understood, but several factors are believed to contribute to its development:


  • Immature Intestinal Immune System: Premature infants have an immature gastrointestinal tract, including an underdeveloped mucosal barrier and an inadequate immune response. This immaturity predisposes them to inflammation and susceptibility to intestinal injury.


  • Enteral Feeding: The introduction of enteral feeding (feeding through the gastrointestinal tract) in premature infants, particularly with formula feeding, has been associated with an increased risk of NEC. The immaturity of the infant’s gut may lead to difficulty in digesting and absorbing nutrients, increasing susceptibility to inflammation and injury.


  • Bacterial Colonization: Alterations in the intestinal microbiota, including bacterial overgrowth or colonization by pathogenic bacteria, may contribute to the development of NEC. The presence of bacteria in the intestinal lumen can trigger an inflammatory response, leading to mucosal damage and necrosis.


  • Ischemia and Hypoxia: Reduced blood flow to the intestines, either due to impaired circulation or hypoxemia (low oxygen levels), can result in ischemia (lack of blood supply) and tissue injury. Premature infants are particularly vulnerable to ischemic insults due to their immature cardiovascular system and susceptibility to hypoxia.


  • Immune System Dysregulation: Abnormalities in the infant’s immune system, including exaggerated inflammatory responses or impaired immune defenses, may contribute to the pathogenesis of NEC. Dysregulation of inflammatory cytokines and immune mediators can lead to tissue damage and necrosis in the intestines.


What is the relationship between NEC and oxidative stress?

The relationship between necrotizing enterocolitis (NEC) and oxidative stress involves complex interactions between intestinal inflammation, ischemia-reperfusion injury, and the generation of reactive oxygen species (ROS) within the intestinal mucosa. While the exact mechanisms linking NEC to oxidative stress are not fully understood, several factors suggest potential connections between these processes:


  • Intestinal Inflammation: NEC is characterized by severe inflammation of the intestinal mucosa, leading to tissue injury and necrosis. Inflammatory cells such as neutrophils and macrophages are activated in response to microbial invasion and tissue damage, leading to the production of ROS as part of the immune response. ROS generated by inflammatory cells contribute to oxidative stress within the intestinal tissue, exacerbating tissue injury and necrosis.


  • Ischemia-Reperfusion Injury: Ischemia-reperfusion injury occurs when blood flow to the intestines is temporarily disrupted (ischemia) and then restored (reperfusion), leading to tissue damage and inflammation. During ischemia, the lack of oxygen and nutrients results in cellular hypoxia and metabolic dysfunction, leading to the generation of ROS within the intestinal tissue. Upon reperfusion, the sudden influx of oxygen-rich blood to the ischemic tissue can further exacerbate oxidative stress, leading to cellular damage and necrosis.


  • Immature Antioxidant Defenses: Premature infants, who are most commonly affected by NEC, have immature antioxidant defenses and are particularly susceptible to oxidative stress. The premature neonatal intestine may have reduced levels of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase, making it more vulnerable to oxidative damage. The imbalance between ROS production and antioxidant defenses contributes to oxidative stress and tissue injury in NEC.


  • Enteral Feeding: The introduction of enteral feeding, particularly formula feeding, has been associated with an increased risk of NEC. Formula feeding may lead to dysbiosis (imbalance in gut microbiota) and alterations in the intestinal microbiome, contributing to intestinal inflammation and oxidative stress. The presence of nutrients and microbial antigens in the intestinal lumen can trigger immune responses and ROS production by inflammatory cells, exacerbating oxidative stress and tissue injury.


  • Gut Microbiota: Dysbiosis and alterations in the gut microbiota composition have been implicated in the pathogenesis of NEC. Disruption of the normal microbial balance in the intestine can lead to increased production of ROS by pathogenic bacteria and reduced levels of beneficial commensal bacteria, further contributing to oxidative stress and intestinal inflammation.


Overall, oxidative stress plays a significant role in the pathogenesis of necrotizing enterocolitis, contributing to intestinal inflammation, tissue injury, and necrosis.