Section for Comparative Pediatrics and Nutrition, Department of Veterinary and Animal Sciences, University of Copenhagen, Denmark.
Plasma-derived therapies, Baxalta Innovations GmbH, Austria, part of Takeda Pharmaceuticals Ltd.
Biomed Pharmacother. 2024 Oct;179:117391. doi: 10.1016/j.biopha.2024.117391. Epub 2024 Sep 5.
Necrotizing enterocolitis (NEC) is a microbiota- and feeding-related gut inflammatory disease in preterm infants. The standard of care (SOC) treatment for suspected NEC is antibiotic treatment and reduced enteral feeding, but how SOC treatment mitigates NEC remains unclear. We explored whether SOC treatment alone or combined with an anti-inflammatory protein (inter-alpha inhibitor protein, IAIP) supplementation improves outcomes in a preterm piglet model of formula-induced NEC. Seventy-one cesarean-delivered preterm piglets were initially fed formula, developing NEC symptoms by day 3, and then randomized into CON (continued feeding) or SOC groups (feeding cessation and antibiotics), each with or without human IAIP (2×2 factorial design). By day 5, IAIP treatment did not significantly influence outcomes, whereas SOC treatment effectively reduced NEC lesions, diarrhea, and bloody stools. Notably, SOC treatment improved gut morphology and function, dampened gut inflammatory responses, altered the colonic microbiota composition, and modulated systemic immune responses. Plasma proteomic analysis revealed the effects of SOC treatment on organ development and systemic inflammatory responses. Collectively, these findings suggest that SOC treatment significantly prevents NEC progression in preterm piglets via effects on gut structure, function, and microbiota, as well as systemic immune and inflammatory responses. Timely feeding cessation and antibiotics are critical factors in preventing NEC progression in preterm infants, while the benefits of additional human IAIP treatment remain to be established.
坏死性小肠结肠炎（NEC）是一种与早产儿肠道微生物群和喂养相关的炎症性疾病。疑似 NEC 的标准治疗（SOC）是抗生素治疗和减少肠内喂养，但 SOC 治疗如何减轻 NEC 仍不清楚。我们探索了 SOC 治疗单独或联合使用抗炎蛋白（α-抑制蛋白，IAIP）补充是否能改善配方诱导的 NEC 早产仔猪模型的结局。71 头剖宫产早产儿最初喂食配方奶，第 3 天出现 NEC 症状，然后随机分为 CON（继续喂养）或 SOC 组（停止喂养和使用抗生素），每组均有或没有人类 IAIP（2×2 析因设计）。到第 5 天，IAIP 治疗并未显著影响结局，而 SOC 治疗可有效减少 NEC 病变、腹泻和血便。SOC 治疗显著改善了肠道形态和功能，减轻了肠道炎症反应，改变了结肠微生物群组成，并调节了全身免疫反应。血浆蛋白质组学分析显示 SOC 治疗对器官发育和全身炎症反应的影响。综上所述，这些发现表明 SOC 治疗通过对肠道结构、功能和微生物群以及全身免疫和炎症反应的影响，显著预防了早产仔猪 NEC 的进展。及时停止喂养和使用抗生素是预防早产儿 NEC 进展的关键因素，而额外使用人类 IAIP 治疗的益处仍有待确定。
