Background: Necrotizing enterocolitis (NEC) is a manifestation of maladaptive intestinal responses in preterm infants centrally medicated by unattenuated inflammation. Early in the postnatal period, preterm infants develop a deficit in arachidonic and docosahexaenoic acid, both potent regulators of inflammation. We hypothesized that the fatty acid composition of parenteral lipid emulsions uniquely induces blood and intestinal fatty acid profiles which, in turn, modifies the risk of NEC development. Methods: 42 preterm pigs were randomized to receive one of three lipid emulsions containing 100% soybean oil (SO), 15% fish oil (MO15), or 100% fish oil (FO100) with enteral feedings over an 8-day protocol. Blood and distal ileum tissue were collected for fatty acid analysis. The distal ileum underwent histologic, proteomic, and metabolomic analyses. Results: Eight pigs (3/14 SO (21 %), 3/14 MO15 (21%), and 2/14 FO100 (14%)) developed NEC. No differences in NEC risk were evident between groups despite differences in induced fatty acid profiles in blood and ileal tissue. Metabolomic analysis of NEC vs no NEC tissue revealed differences in tryptophan metabolism and arachidonic acid-containing glycerophospholipids. Proteomic analysis demonstrated no differences by lipid group; however, 15 proteins differentiated NEC vs no NEC in the domains of tissue injury, glucose uptake and chemokine signaling. Conclusions: Exposure to parenteral lipid emulsions induces unique intestinal fatty acid and metabolomic profiles, however, these profiles are not linked to a difference in NEC development. Metabolomic and proteomic analyses of NEC vs no NEC intestinal tissue provide mechanistic insights into the pathogenesis of NEC in preterm infants.

中文翻译：

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肠外脂质乳剂可诱导独特的回肠脂肪酸和代谢组学特征，但不会增加早产猪坏死性小肠结肠炎的风险

背景：坏死性小肠结肠炎 (NEC) 是由未减轻炎症集中治疗的早产儿肠道适应不良反应的一种表现。在产后早期，早产儿缺乏花生四烯酸和二十二碳六烯酸，两者都是炎症的有效调节剂。我们假设肠外脂质乳剂的脂肪酸成分独特地诱导血液和肠道脂肪酸谱，进而改变 NEC 发展的风险。方法：42 头早产猪随机接受三种脂肪乳剂中的一种，其中含有 100% 大豆油 (SO)、15% 鱼油 (MO15) 或 100% 鱼油 (FO100)，在为期 8 天的方案中进行肠内喂养。收集血液和远端回肠组织用于脂肪酸分析。远端回肠进行了组织学、蛋白质组学和代谢组学分析。结果：八头猪（3/14 SO (21%)、3/14 MO15 (21%) 和 2/14 FO100 (14%)）出现 NEC。尽管血液和回肠组织中诱导的脂肪酸谱存在差异，但各组之间的 NEC 风险没有明显差异。NEC 与无 NEC 组织的代谢组学分析揭示了色氨酸代谢和含有花生四烯酸的甘油磷脂的差异。蛋白质组学分析表明脂质组没有差异；然而，在组织损伤、葡萄糖摄取和趋化因子信号传导领域，有 15 种蛋白质区分 NEC 与没有 NEC。结论：暴露于肠外脂质乳剂会诱导独特的肠道脂肪酸和代谢组学特征，然而，这些特征与 NEC 发展的差异无关。