Sangild Per T, Siggers Richard H, Schmidt Mette, Elnif Jan, Bjornvad Charlotte R, Thymann Thomas, Grondahl Marie L, Hansen Axel K, Jensen Soeren K, Boye Mette, Moelbak Lars, Buddington Randal K, Weström Björn R, Holst Jens J, Burrin Douglas G
Divisions of Nutrition and Reproduction, Royal Veterinary and Agricultural University, Frederiksberg, Denmark.
Gastroenterology. 2006 May;130(6):1776-92. doi: 10.1053/j.gastro.2006.02.026.
BACKGROUND & AIMS: Preterm birth and formula feeding are key risk factors associated with necrotizing enterocolitis (NEC) in infants, but little is known about intestinal conditions that predispose to disease. Thus, structural, functional, and microbiologic indices were used to investigate the etiology of spontaneous NEC development in preterm pigs.
Piglets were delivered by cesarean section at 92% gestation, reared in infant incubators, and fed infant formula or colostrum every 3 hours (n = 120) until tissue collection at 1-2 days of age.
Clinical and histopathologic signs of NEC were observed in 57% of pigs fed FORMULA (26/46) and in 5% of pigs fed COLOSTRUM (2/38) (P < .05). Relative to COLOSTRUM, both healthy and sick FORMULA pigs had reduced intestinal villous heights, enzyme activities, nutrient absorption, and antioxidant levels and higher inducible nitric oxide synthetase activity (P < .05). In healthy pigs, mucosal microbial diversity remained low and diet independent. NEC pigs showed bacterial overgrowth, and a high mucosal density of Clostridium perfringens was detected in some but not all pigs. Germ-free conditions and antiserum against Clostridium perfringens toxin prevented intestinal dysfunction and NEC in formula-fed pigs, whereas the gut trophic factors, epidermal growth factor, and glucagon-like peptide 2 had limited effects.
A subclinical, formula-induced mucosal atrophy and dysfunction predispose to NEC and bacterial overgrowth. The adverse feeding effects are colonization dependent and may be reduced by factors in colostrum that include antibodies against aggressive toxins such as those of Clostridium perfringens.
早产和配方奶喂养是婴儿坏死性小肠结肠炎（NEC）的关键危险因素，但对于易引发该疾病的肠道状况知之甚少。因此，本研究利用结构、功能和微生物学指标来探究早产仔猪自发性NEC发生发展的病因。
在妊娠92%时通过剖宫产分娩仔猪，将其饲养在婴儿培养箱中，每3小时喂一次婴儿配方奶或初乳（n = 120），直至1 - 2日龄时采集组织。
喂食配方奶的猪中有57%（26/46）出现了NEC的临床和组织病理学症状，而喂食初乳的猪中这一比例为5%（2/38）（P <.05）。相对于初乳，无论是健康还是患病的配方奶喂养猪，其肠绒毛高度、酶活性、营养物质吸收和抗氧化水平均降低，诱导型一氧化氮合酶活性升高（P <.05）。在健康猪中，黏膜微生物多样性较低且与饮食无关。NEC猪表现出细菌过度生长，部分但并非所有猪中检测到产气荚膜梭菌的黏膜密度较高。无菌条件和抗产气荚膜梭菌毒素的抗血清可预防配方奶喂养猪的肠道功能障碍和NEC，而肠道营养因子、表皮生长因子和胰高血糖素样肽2的作用有限。
亚临床的、配方奶诱导的黏膜萎缩和功能障碍易引发NEC和细菌过度生长。不良喂养效应依赖于细菌定植，初乳中的某些因素（包括针对产气荚膜梭菌等侵袭性毒素的抗体）可能会减轻这些效应。
