Fusing Glycobiology and Nutritional Sciences to Prevent Necrotizing Enterocolitis

K99奖第一年的项目期截止于2009年3月1日。我目前在一年级还是K99大奖。由于距离上次报告只过去了很短的时间，除了第一年的进度报告外，凌晨1点只提供了简短的最新情况。 在前一份报告中，我描述了在大鼠NEC模型中进行的第一组INTEN/INTENTING研究的初步数据。为了增加每组动物的数量，并能够计算出意义，我们用更多的分析重复了这项干预研究。下图显示，接受不含HMO配方奶粉的大鼠发生了NEC，平均病理评分为1.98？0.34。病理评分明显降低至0.79±0.39。当配方中添加0.1、1和10 mg/mLHMO时，分别为0.64±0.54和0.44±0.30。0.1 mg/m L和10 m g/m L的浓度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。母乳喂养的幼鼠的平均得分只有0.15±0.34，这与服用HMO配方奶粉的大鼠没有显著差异。 这是第一个在动物疾病模型中显示HMO显著降低NEC的活体数据。这一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阶段的开始，我们将继续进行特定目标1中提出的实验，分析HMO是否改变粘膜中性粒细胞的渗透和激活，以及HMO是否改变肠屏障功能。之后，我们将继续具体的目标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.