75) and elicits immune responses through the nuclear factor (NF)-κB pathway (Ref. 76). NOD-2 activity may exert protective effects in NEC as daily injections of MDP almost completely abolished NEC-associated intestinal tissue damage in mice (Ref. 77). Similarly, in humans, NOD-2 loss-of-function mutations has been associated with Crohn's disease (CD) (Refs 78, 79) and VLBW infant carriers of two or more NOD-2 loss-of-function alleles had an increased risk for NEC requiring surgery (OR 3.57; 95% CI 1.3–10.0, P = 0.03) (Ref. 80). This evidence concerns the gene NOD2 and Crohn disease.