Department of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.
Am J Physiol Gastrointest Liver Physiol. 2011 Sep;301(3):G435-45. doi: 10.1152/ajpgi.00400.2010. Epub 2011 Jun 23.
Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly from a mild intolerance to enteral feeding into intestinal mucosal hemorrhage, inflammation, and necrosis. We hypothesized that immediate feeding-induced gut responses precede later clinical NEC symptoms in preterm pigs. Fifty-six preterm pigs were fed total parenteral nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17, or 34 h with either colostrum (Colos, n = 20) or formula (Form, n = 31). Macroscopic NEC lesions were detected in Form pigs throughout the enteral feeding period (20/31, 65%), whereas most Colos pigs remained protected (1/20, 5%). Just 8 h of formula feeding induced histopathological lesions, as evidenced by capillary stasis and necrosis, epithelial degeneration, edema, and mucosal hemorrhage. These immediate formula-induced changes were paralleled by decreased digestive enzyme activities (lactase and dipeptidylpeptidase IV), increased nutrient fermentation, and altered expression of innate immune defense genes such as interleukins (IL-1α, IL-6, IL-18), nitric oxide synthetase, tight junction proteins (claudins), Toll-like receptors (TLR-4), and TNF-α. In contrast, the first hours of colostrum feeding induced no histopathological lesions, increased maltase activity, and induced changes in gene expressions related to tissue development. Total bacterial density was high after 2 days of parenteral feeding and was not significantly affected by diet (colostrum, formula) or length of enteral feeding (8-34 h), except that a few bacterial groups (Clostridium, Enterococcus, Streptococcus species) increased with time. We conclude that a switch from parenteral to enteral nutrition rapidly induces diet-dependent histopathological, functional, and proinflammatory insults to the immature intestine. Great care is required when introducing enteral feeds to TPN-fed preterm infants, particularly when using formula, because early feeding-induced insults may predispose to NEC lesions that are difficult to revert by later dietary or medical interventions.
坏死性小肠结肠炎（NEC）在早产儿中从对肠内喂养的轻度不耐受迅速发展为肠黏膜出血、炎症和坏死。我们假设，在早产儿中，立即发生的喂养诱导的肠道反应先于后期临床 NEC 症状。56 只早产儿接受全胃肠外营养（TPN）48 小时后，再接受母乳（Colos，n=20）或配方奶（Form，n=31）喂养 0、8、17 或 34 小时。在整个肠内喂养期间，所有接受配方奶喂养的仔猪都出现了宏观坏死性小肠结肠炎病变（20/31，65%），而大多数接受母乳的仔猪仍然受到保护（1/20，5%）。仅仅 8 小时的配方奶喂养就会导致组织病理学损伤，表现为毛细血管淤滞和坏死、上皮变性、水肿和黏膜出血。这些立即发生的配方奶诱导的变化与消化酶活性（乳糖酶和二肽基肽酶 IV）降低、营养物发酵增加以及先天免疫防御基因（白细胞介素[IL]-1α、IL-6、IL-18）、一氧化氮合酶、紧密连接蛋白（紧密连接蛋白）、Toll 样受体（TLR-4）和 TNF-α的表达改变相平行。相比之下，最初几小时的母乳喂养不会引起组织病理学损伤，反而会增加麦芽糖酶活性，并诱导与组织发育相关的基因表达改变。肠外喂养 2 天后，总细菌密度很高，不受饮食（母乳、配方奶）或肠内喂养时间（8-34 小时）的显著影响，但少数细菌群（梭菌、肠球菌、链球菌属）随时间增加。我们得出结论，从肠外营养向肠内营养的转变会迅速引起不成熟肠道依赖于饮食的组织病理学、功能和促炎损伤。当早产儿从 TPN 喂养转为肠内喂养时，需要特别小心，尤其是在使用配方奶时，因为早期喂养诱导的损伤可能导致难以通过后期饮食或医疗干预逆转的 NEC 病变。
