Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
Diet Modulates the High Sensitivity to Systemic Infection in Newborn Preterm Pigs
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DOI：
10.3389/fimmu.2020.01019
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发表时间：
2020-05-27
影响因子：
7.3
通讯作者：
Sangild, Per Torp
中科院分区：
文献类型：
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作者：
Baek, Ole;Brunse, Anders;Sangild, Per Torp
背景：早产儿出生时免疫系统不成熟，被动免疫能力有限，出生后有发生菌血症和败血症的风险。我们假设，无论添加或不添加免疫球蛋白，肠内喂养都能改善凝固酶阴性葡萄球菌引起的全身感染的临床反应。方法：以早产剖宫产猪为早产儿模型，在出生后0-3天系统地输注活体表皮葡萄球菌(SE，每公斤5×10(9)个集落形成单位)。在出生时不同的胎龄(早产儿和足月儿)、肠内奶饮食(牛初乳、添加或不添加猪血浆的婴儿配方奶粉)以及添加/不添加全身免疫球蛋白后，对硒感染的反应进行了评估。对感染SE的猪进行12-48h的临床变量、血液细菌学、化学、血液学和肠道功能障碍(肠道通透性、坏死性小肠结肠炎病变)的评估。结果：出生后不久感染SE的早产猪与足月猪相比，出现了不良的临床反应和死亡率增加。与饲喂婴儿配方奶粉的猪相比，出生后立即饲喂牛初乳可以改善血液中SE的清除和临床状态(改善体力活动和肠道结构，减少骨髓细菌)。几天后，临床对SE菌血症(血液学、中性粒细胞吞噬能力、T细胞亚群)的反应不那么严重，不同的牛奶日粮对SE菌血症的影响较小，无论是否添加免疫球蛋白。结论：早产儿增加了新生猪对SE菌血症的敏感性，可能导致败血症。对系统性SE感染的敏感度在早产后几天迅速下降。年龄和饮食(肠外营养、初乳、牛奶、配方奶)都可能影响早产儿出生后几天的肠道炎症、细菌易位和系统免疫发育。
Background: Preterm infants are born with an immature immune system, limited passive immunity, and are at risk of developing bacteremia and sepsis in the postnatal period. We hypothesized that enteral feeding, with or without added immunoglobulins, improves the clinical response to systemic infection by coagulase negative staphylococci.Methods: Using preterm cesarean delivered pigs as models for preterm infants, we infused live Staphylococcus epidermidis (SE, 5 x 10(9) colony forming units per kg) systemically 0-3 days after birth across five different experiments. SE infection responses were assessed following different gestational age at birth (preterm vs. term), enteral milk diets (bovine colostrum, infant formula with or without added porcine plasma) and with/without systemic immunoglobulins. Pigs infected with SE were assessed 12-48 h for clinical variables, blood bacteriology, chemistry, hematology, and gut dysfunction (intestinal permeability, necrotizing enterocolitis lesions).Results: Adverse clinical responses and increased mortality were observed in preterm vs. term pigs, when infected with SE just after birth. Feeding bovine colostrum just after birth improved blood SE clearance and clinical status (improved physical activity and intestinal structure, fewer bone marrow bacteria), relative to pigs fed infant formula. A few days later, clinical responses to SE bacteremia (hematology, neutrophil phagocytic capacity, T cell subsets) were less severe, and less affected by different milk diets, with or without added immunoglobulins.Conclusion: Prematurity increases the sensitivity of newborn pigs to SE bacteremia, potentially causing sepsis. Sensitivity to systemic SE infection decreases rapidly in the days after preterm birth. Both age and diet (parenteral nutrition, colostrum, milk, formula) may influence gut inflammation, bacterial translocation and systemic immune development in the days after birth in preterm newborns.