Sialylated galacto-oligosaccharides and 2-fucosyllactose reduce necrotising enterocolitis in neonatal rats

Sialylated galacto-oligosaccharides and 2-fucosyllactose reduce necrotising enterocolitis in neonatal rats
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DOI:
10.1017/s0007114516002038
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发表时间:
2016-07-28
影响因子:
3.6
通讯作者:
Bode, Lars
Bode, Lars
中科院分区:
医学3区
文献类型:
--
作者:
Autran, Chloe A.;Schoterman, Margriet H. C.;Bode, Lars

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坏死性小肠结肠炎(NEC)是早产儿中最常见和最致命的肠道疾病之一,治疗选择非常有限。母乳喂养的婴儿的NEC风险比配方奶粉喂养的婴儿低6-10倍,我们之前已经证明母乳低聚糖(HMO)可以改善大鼠NEC模型的生存率并减少病理学。HMO二唾液酸乳糖-N-四糖(DSLNT)是最有效的,唾液酸化被证明是必不可少的保护作用。低聚半乳糖(GOS),目前添加到一些婴儿配方奶粉,但不含唾液酸,没有影响。除了DSLNT之外,我们之前的工作还表明,含有高浓度2-岩藻糖基乳糖(2FL)的中性HMO组分略微改善了病理学评分。在这里,我们评估了2FL以及我们酶促唾液酸化的GOS(Sia-GOS)的体内功效。将新生大鼠随机分为以下研究组-母鼠喂养(DF)、配方奶喂养(FF)、含有混合HMO(10 mg/ml)、GOS(8 mg/ml)、Sia-GOS(500 μ m)或2FL(2 mg/ml)的FF,并进行已建立的NEC方案。DF和HMO组的病理学评分最低,平均值分别为067(sd 034)和090(sd 047)。FF组的病理学评分显著升高,为202(sd 063)。虽然在配方中添加GOS没有保护作用,并且产生200分(sd 063),但添加Sia-GOS或2FL显著降低病理学评分至132分(sd 056)(P
Necrotising enterocolitis (NEC) is one of the most frequent and fatal intestinal disorders in preterm infants and has very limited treatment options. Breast-fed infants are at a 6-10-fold lower NEC risk than formula-fed infants, and we have previously shown that human milk oligosaccharides (HMO) improved survival and reduced pathology in a rat NEC model. The HMO disialyllacto-N-tetraose (DSLNT) was most effective, and sialylation was shown to be essential for its protective effect. Galacto-oligosaccharides (GOS), currently added to some infant formula, but not containing sialic acid, had no effect. In addition to DSLNT, our previous work also showed that the neutral HMO fraction, which contains high concentrations of 2-fucosyllactose (2FL), slightly improved pathology scores. Here, we assessed the in vivo efficacy of 2FL, as well as of GOS that we enzymatically sialylated (Sia-GOS). Neonatal rats were randomised into the following study groups - dam-fed (DF), formula-fed (FF), FF containing pooled HMO (10 mg/ml), GOS (8 mg/ml), Sia-GOS (500 mu m) or 2FL (2 mg/ml) - and subjected to the established NEC protocol. The DF and HMO groups had the lowest pathology scores with mean values of 067 (sd 034) and 090 (sd 047), respectively. The FF group had significantly elevated pathology scores of 202 (sd 063). Although the addition of GOS to the formula had no protective effect and generated scores of 200 (sd 063), the addition of Sia-GOS or 2FL significantly lowered pathology scores to 132 (sd 056) (P