TLR4 and necrotizing enterocolitis: In animal models, administration of probiotics enriched with bacterial DNA, particularly CpG DNA motifs, leads to the activation of Toll-like receptor 9 (TLR9), which serves as a negative regulator of the TLR4 signaling cascade in enterocytes, thus reducing the lipopolysaccharide (LPS)-mediated TLR4 signaling.62,63 This modulation of the immune response is thought to attenuate the severity of NEC.