Prevention of Necrotizing Enterocolitis through Milk Polar Lipids Reducing Intestinal Epithelial Apoptosis

Abstract

Neonatal necrotizing enterocolitis (NEC) is a common and devastating disease. The objective of this research was to investigate the protective mechanisms of milk polar lipids (MPLs) on the attenuation of lipopolysaccharides (LPS)-induced intestinal inflammation and apoptosis. MPLs were extracted from buttermilk and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A neonatal NEC rat model was used to investigate the effects of MPLs on NEC and its underlying mechanisms. Hematoxylin−eosin (H&E) staining and terminal deoxynucleotidyl transferasemediated dUTP-biotin nick-end labeling (TUNEL) assay were used to observe intestinal morphological changes and intestinal epithelial cell apoptosis, which showed that MPLs could reduce NEC symptoms and intestinal apoptosis. The expressions of IL-6, IL-8, and TNF-α in the MPL group was significantly downregulated (P < 0.05), and the expression levels of IL-10 were significantly upregulated (P < 0.05). At the same time, MPLs also significantly reduced (P < 0.05) activation of the LPS-induced TLR4/NF-κB signaling pathway. Furthermore, MPLs inhibit apoptosis by reducing the expressions of Bax, caspase-9, and caspase-3 and by increasing the expression of Bcl-2. In conclusion, MPLs could reduce NEC symptoms in mice by inhibiting cell inflammation and protecting against intestinal apoptosis.

Enteral Feeding Interventions in the Prevention of Necrotizing Enterocolitis: A Systematic Review of Experimental and Clinical Studies

“…Enteral treatment with MPL, which are abundantly present in MFGM, increased intestinal IL10 protein expression, while decreasing intestinal TNFα, IL6 and IL8 protein expression and TLR4 immunoreactivity [84]. In addition, MPL inhibited NEC induced intestinal p65 and p50 expression [84]. Pomegranate seed oil, rich in unsaturated fatty acids such as conjugated linolenic acids and oleic acid, blocks an increase in ileal gene expression of IL6, IL8, IL12, interleukin 23 (IL23) and TNFα in neonatal rats during NEC [47].…”

“…Enteral supplementation of bovine MFGM reduces ileal mRNA expression of IL1β, TNFα and IL6, as well as protein expression of TLR4 [48], whereas TLR9 signaling remained unaffected [48]. Enteral treatment with MPL, which are abundantly present in MFGM, increased intestinal IL10 protein expression, while decreasing intestinal TNFα, IL6 and IL8 protein expression and TLR4 immunoreactivity [84]. In addition, MPL inhibited NEC induced intestinal p65 and p50 expression [84].…”

“…Fish oil (rich in n-3 PUFA) [82,83] MPL [84] MFGM [48] Very low fat diet [85] Reduced long chain triacylglycerol diet (considered pre-digested) [85] Pomegranate seed oil [47] Carbohydrate/sugar-based interventions HMO [38,42,49,[86][87][88][89][90] Neutral HMO (no sialic acids) [42] −2 HMO (two sialic acids) [42] DSLNT (HMO) [42] DSLNnT (synthetic disialyl glycan) [89,90] DS'LNnT (synthetic disialyl glycan) [89,90] 2 -FL [87,91,92] 6 -SL [92] 2 -FL and 6 -SL [42,92] Sialylated HMO [93] Sialylated GOS [87] GD3 [50] Hyaluronan 35 kD [94] Protein/amino acid-based interventions L-Glutamine/glutamine [84,[95][96][97] Arginine [98,99] L-Carnitine [99] N-Acetylcysteine [85] Lactadherin [51] OPN [100] Lactoferrin [101] IAP [102,103] [104] HB-EGF [41,[58]…”

Lipid Composition, Digestion, and Absorption Differences among Neonatal Feeding Strategies: Potential Implications for Intestinal Inflammation in Preterm Infants

“…In a neonatal rat model of NEC induced by hypoxia and hypothermia, formula-fed pups supplemented with bovine MFGM demonstrated increased weight gain, reductions in NEC incidence and mortality, and a decrease in intestinal damage as compared with pups fed formula alone [185]. Yang et al reported that treatment of neonatal rats with a bovine milk polar lipid extraction, including both sphingolipids and phospholipids, reduced NEC symptoms through a reduction in both apoptosis and inflammation in the intestinal epithelium [186]. Though supplementation of bovine MFGM does not address the discrepancy in MFG size between infant formula and HM, the individual protein, sphingolipid, and phospholipid components of the MFGM clearly exert positive physiological influences in the postnatal environment [22].…”

Prevention and Curation of DSS-induced IBD&nbsp;in Mice With Bacillus Subtilis Fermented Milk via Inhibition of the Inflammatory Responses and Regulation of the Intestinal Flora

“…CLA could ameliorate DSS-induced colitis in mice model, 28 and MPLs could ameliorate necrotizing enterocolitis (NEC) in rat model by inhibiting the in ammatory response. 29 Lorea et al reported that the yogurt contained probiotics possessed anti-in ammatory effects in IBD patients. 30 These reports prompt that the B. subtilis fermented milk might be applied as a functional food for prevention and curation of IBD in the future.…”