The engagement of TLR4 leads to a downregulation of eNOS, an enzyme integral to nitric oxide synthesis.77 Consequently, the reduced production of nitric oxide – a key vasodilator – facilitates the mesenteric vessels to vasoconstriction, thereby promoting the intestine to ischemia, a hallmark of NEC.77 These findings illustrate the critical interplay between the intestinal microbiota and the immature vascular endothelium in impairing intestinal perfusion, a significant factor in the progression of NEC. This evidence concerns the gene NOS3 and necrotizing enterocolitis.