Fusing Glycobiology and Nutritional Sciences to Prevent Necrotizing Enterocolitis

K99奖第一年的项目期于3月1日结束。2009.我目前在第一年或K99奖。由于上一次报告的时间很短，除了第一年的进度报告外，我只提供了一个简短的更新。 在前一份报告中，我描述了在大鼠NEC模型中进行的第一组干预研究的初步数据。为了增加每组动物的数量并能够计算显著性，我们用更多的动物重复了干预研究。下图显示，接受不含HMO的配方奶粉的大鼠发生NEC，平均病理学评分为1.98 ± 0.34。病理学评分显著降低至0.79 <$0.39。当配方中分别添加0.1、1和10 mg/mL HMO时，分别为0.64 <$0.54和0.44 <$0.30。0.1和10 mg/mL的范围分别与大鼠和人乳中的HMO浓度相似。没有一只接受HMO的大鼠的病理学评分高于接受不含HMO的配方奶粉的大鼠的平均评分。母乳喂养的幼崽平均得分仅为0.15 - 0.34，与接受HMO配方的大鼠没有显著差异。 这是第一个显示HMO在动物疾病模型中显著降低NEC的体内数据。这些数据证实了我们最初的假设，并证明了最初为该奖项的ROO阶段提出的所有未来实验的合理性。在ROO阶段开始时，我们将继续具体目标1中提出的实验，并分析HMO是否改变粘膜中性粒细胞浸润和活化以及HMO是否改变肠屏障功能。然后，我们将继续讨论具体目标2、3和4。

The Project Period tor Year 1 of the K99 Award ended March 1. 2009. I am currently in Year i or the K99 Award. Since only a short time has passed since the last report, 1 am only providing a brief update in addition to the Progress Report for Year 1. In the previous report, I described preliminary data from the first set of inten/ention studies In the rat NEC model. To increase the number of animals per group and to be able to calculate significances, we repeated the' intervention study with more anlmials. The figure below shows that rats receiving formula without HMO developed NEC with an average pathology score of 1.98¿0.34. The pathology score was significantly reduced to 0.79¿0.39. 0.64¿0.54 and 0.44¿0.30 when the formula was supplemented with HMO at 0.1, 1, and 10 mg/mL, respectively. The range of 0.1 and 10 mg/mL resembles the HMO concentration in rat and human milk, respectively. None of the rats that received HMO had a pathology score that was higher than the average score of rats that received formula without HMO. Breast-fed pups had an average score of only 0.15¿0.34, which was not significantly different from rats that received HMO with their formula. This is the first in vivo data showing that HMO significantly reduce NEC In an animal disease model. This data confirms our initial hypothesis and justifies all future experiments originally proposed for the ROO phase of the award. In the beginning of the ROO phase, we will continue with the experiments proposed in Specific Aim 1 and analyze whether HMO alter mucosal neutrophil infiltration and activation and whether HMO alter the intestinal barrier function. Afterwards, we will move on to Specific Aim 2, 3 and 4.