Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.
Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.
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DOI：
10.1016/j.jpeds.2017.01.013
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Viscardi RM
中科院分区：
文献类型：
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作者：
Saleem B;Okogbule-Wonodi AC;Fasano A;Magder LS;Ravel J;Kapoor S;Viscardi RM
为了检验喂养和抗生素暴露影响早产儿肠屏障成熟的假设，我们连续测量了出生后前两周内<33周妊娠（GA）婴儿的肠通透性（IP）生物标志物。在IP生物标志物的前瞻性研究（NCT 01756040）中，在出生后4天内招募符合条件的<33周GA的婴儿。研究参与者在研究第1、8和15天肠内接受非代谢糖乳果糖/鼠李糖（La/Rh），并通过HPLC测量尿液中的La/Rh。血清zonulin和粪便α-1抗胰蛋白酶，其他两个IP标记物，分别通过半定量蛋白质印迹和ELISA测定。在43例受试者的队列中，La/Rh比值在第1天升高，并在2周内下降，但与> 28 wk GA的婴儿IP相比，GA ≤28 wk的婴儿的La/Rh比值仍较高。纯母乳喂养与肠屏障功能的更快成熟相关。对所有时间点采集尿样的35例受试者进行的聚类分析显示了三种IP模式（聚类1，正常成熟[N=20（57%）];聚类2，第一周IP降低，随后大幅增加[N=5（14%）];聚类3，成熟延迟[N=10（29%）]）。有延长抗生素暴露时间（p=0.092）和延迟开始喂养≥4天（p= 0.092）的趋势。0.064）。早产儿的肠屏障成熟是GA和出生后年龄依赖性的，并受到母乳喂养的成熟效应喂养的影响，可能是抗生素暴露。
To test the hypothesis that feeding and antibiotic exposures affect intestinal barrier maturation in preterm infants, we serially measured intestinal permeability (IP) biomarkers in infants <33 wks gestation (GA) during the first two weeks of life. Eligible infants <33 wks GA were enrolled within 4 days of birth in a prospective study of IP biomarkers (NCT01756040). Study participants received the non-metabolized sugars lactulose/rhamnose (La/Rh) enterally on study days 1, 8 and 15 and La/Rh were measured in urine by HPLC. Serum zonulin and fecal alpha-1 antitrypsin, two other IP markers, were measured by semi-quantitative western blot and ELISA, respectively. In a cohort of 43 subjects, the La/Rh ratio was elevated on day 1 and decreased over 2 weeks, but remained higher in infants ≤28 wk GA compared with IP in infants >28 wk GA. Exclusive breastmilk feeding was associated with more rapid maturation in intestinal barrier function. A cluster analysis of 35 subjects who had urine samples from all time points revealed three IP patterns (Cluster 1, normal maturation [N=20 (57%)]; Cluster 2, decreased IP during the first week and subsequent substantial increase [N=5 (14%)]; and Cluster 3, delayed maturation [N=10 (29%)]). There were trends towards more prolonged antibiotic exposure (p=0.092) and delayed initiation of feeding ≥4 days (p=0. 0.064) in infants with abnormal IP patterns. Intestinal barrier maturation in preterm infants is GA and postnatal age-dependent and is influenced by feeding with a maturational effect of breastmilk feeding and may be by antibiotic exposures.