Milk Fat Globule Membrane Ameliorates Necrotizing Enterocolitis in Neonatal Rats and Suppresses Lipopolysaccharide-Induced Inflammatory Response in IEC-6 Enterocytes.

Abstract

Evidence has provided support for the beneficial effects of milk fat globule membrane (MFGM) on inflammation in the intestinal tract. The objective of this study was to investigate the effects of MFGM on a rat model of necrotizing enterocolitis (NEC) and its potential mechanism of action. Sixty-two newborn Sprague Dawley rats were randomly divided into 4 experimental groups: Breast-fed normal, formula fed (FF), FF + 6 g/L MFGM, and FF + 12 g/L MFGM. The FF rats and the FF rats supplemented with MFGM were exposed to asphyxia/cold stress to induce NEC. Body weight, histological score, survival time, oxidative stress injury, enterocyte proliferation/apoptosis, and inflammatory response were assessed. Meanwhile, lipopolysaccharide (LPS)-stimulated IEC-6 enterocytes were used as a model to test the anti-inflammatory effects of MFGM. Supplementation with 12 g/L MFGM alleviated body weight loss, reduced the incidence of NEC, increased the survival rate, and attenuated the severity of bowel damage in the NEC rat model. Furthermore, 12 g/L MFGM administration inhibited the protein expression of toll-like receptor 4 (TLR4) in the animal model. In IEC-6 enterocytes, the upregulation of TLR4, myeloid differentiation primary response gene 88 (MyD88), phosphorylated nuclear factor-κB (NF-κB) p65 subunit, and the nuclear translocation of NF-κBp65 induced by LPS was partially inhibited by MFGM pretreatment. Our findings suggested that MFGM has beneficial effects on neonatal rats with NEC by suppressing inflammation via the TLR4/MyD88/NF-κB pathway.