Department of Human Nutrition, University of Copenhagen, Frederiksberg C, Denmark.
Br J Nutr. 2012 Aug;108(4):672-81. doi: 10.1017/S0007114511006404. Epub 2011 Dec 5.
Preterm neonates show enhanced sensitivity to nutrient maldigestion and bacteria-mediated gut inflammatory disorders, such as necrotising enterocolitis (NEC). We hypothesised that preterm birth increases the sensitivity of intestinal nutrient absorption to endotoxins and that feeding after birth reduces this response. Hence, we investigated the postnatal development of nutrient digestive and absorptive capacity in the preterm and term pig intestine, and its responsiveness to endotoxins. Pigs were delivered by caesarean section at preterm (n 20) or term (n 17) gestation, and the small intestine was collected at birth or after 2 d of colostrum feeding, followed by ex vivo stimulation with lipopolysaccharide endotoxins and mixed gut contents collected from pigs with NEC. Brush border enzyme activities were reduced in newborn preterm v. term pigs (39-45 % reduction, P < 0.05), but normalised after 2 d of feeding. Ex vivo leucine and glucose uptake increased with prenatal age. Bacterial stimulation reduced the nutrient uptake similarly at birth and after 2 d in preterm and term pigs (23-41 % reduction, P < 0.05), whereas IL-6 and TNF-α expression was stimulated only at birth. Toll-like receptor-4 expression increased markedly at day 2 for preterm and term pigs (22-33-fold, P < 0.05) but with much lower expression levels in newborn preterm pigs (approximately 95 %, P < 0.01). In conclusion, digestive and absorptive functions mature in the prenatal period, but are similarly affected by postnatal feeding and bacterial exposure in both preterm and term pigs. Nutrient maldigestion may contribute to NEC development, while a prematurity-related hyper-responsiveness to endotoxins could be less important, at least in pigs.
早产儿对营养消化不良和细菌介导的肠道炎症紊乱(如坏死性小肠结肠炎(NEC))更为敏感。我们假设早产会增加肠道营养吸收对内毒素的敏感性,而出生后的喂养会降低这种反应。因此,我们研究了早产儿和足月产猪肠道的营养消化和吸收能力的产后发育及其对内毒素的反应性。猪通过剖腹产在早产(n=20)或足月(n=17)妊娠时分娩,在出生时或初乳喂养 2 天后收集小肠,并随后用脂多糖内毒素和从患有 NEC 的猪收集的混合肠道内容物进行离体刺激。与足月产猪相比,新生早产儿的刷状缘酶活性降低(39-45%,P<0.05),但在喂养 2 天后恢复正常。产前年龄增加会增加离体亮氨酸和葡萄糖摄取。细菌刺激同样降低了早产和足月猪出生时和 2 天后的营养摄取(23-41%,P<0.05),而只有在出生时才会刺激 IL-6 和 TNF-α 的表达。早产和足月猪的 TLR-4 表达在第 2 天显著增加(22-33 倍,P<0.05),但在新生早产儿中的表达水平要低得多(约 95%,P<0.01)。总之,消化和吸收功能在产前阶段成熟,但在早产和足月猪中,它们都受到产后喂养和细菌暴露的类似影响。营养消化不良可能导致 NEC 发展,而与早产相关的对内毒素的高反应性可能不太重要,至少在猪中是这样。