TLR4 and necrotizing enterocolitis: This in turn indirectly inhibits the TLR4 signaling pathway by reducing enterocyte apoptosis, contributing to the prevention of NEC.70 In a large human study enrolling 9,082 VLBW infants, carriers of two or more NOD2 loss-of-function mutations had a significantly increased risk for NEC requiring surgery, highlighting a potential protective role of NOD2 in the development of NEC.71