Klerk Daphne H, Plösch Torsten, Verkaik-Schakel Rikst Nynke, Hulscher Jan B F, Kooi Elisabeth M W, Bos Arend F
Division of Neonatology, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Front Pediatr. 2021 Mar 4;9:630817. doi: 10.3389/fped.2021.630817. eCollection 2021.
Epigenetic changes, such as DNA methylation, may contribute to an increased susceptibility for developing necrotizing enterocolitis (NEC) in preterm infants. We assessed DNA methylation in five NEC-associated genes, selected from literature: , and in infants with NEC and controls. Observational cohort study including 24 preterm infants who developed NEC (≥Bell Stage IIA) and 45 matched controls. DNA was isolated from stool samples and methylation measured using pyrosequencing. We investigated differences in methylation prior to NEC compared with controls. Next, in NEC infants, we investigated methylation patterns long before, a short time before NEC onset, and after NEC. Prior to NEC, only CpG 2 methylation was increased in NEC infants (median = 75.4%, IQR = 71.3-83.8%) versus controls (median = 69.0%, IQR = 64.5-77.4%, = 0.025). In NEC infants, CpG 3 methylation was 0.8% long before NEC, increasing to 1.8% a short time before NEC and 2.0% after NEC ( = 0.011; = 0.021, respectively). A similar pattern was found in CpG 1, which increased from 75.4 to 81.4% and remained 85.3% ( = 0.027; = 0.019, respectively). These changes were not present for , and . Epigenetic changes of , and are present in NEC infants and can differ in relation to the time of NEC onset. Differences in DNA methylation of , and may influence gene expression and increase the risk for developing NEC. This study also demonstrates the use of human DNA extraction from stool samples as a novel non-invasive method for exploring the bowel of preterm infants and which can also be used for necrotizing enterocolitis patients.
表观遗传变化，如DNA甲基化，可能会导致早产儿患坏死性小肠结肠炎（NEC）的易感性增加。我们评估了从文献中选取的五个与NEC相关基因（此处原文未列出具体基因名称）在NEC婴儿和对照组婴儿中的DNA甲基化情况。观察性队列研究纳入了24例发生NEC（≥Bell IIA期）的早产儿和45例匹配的对照组。从粪便样本中提取DNA，并使用焦磷酸测序法测量甲基化水平。我们研究了NEC婴儿与对照组相比在NEC发生前的甲基化差异。接下来，在NEC婴儿中，我们研究了在NEC发生前很长时间、NEC发作前短时间以及NEC发生后 的甲基化模式。在NEC发生前，与对照组（中位数 = 69.0%，四分位间距 = 64.5 - 77.4%，P = 0.025）相比，NEC婴儿中仅CpG 2甲基化增加（中位数 = 75.4%，四分位间距 = 71.3 - 83.8%）。在NEC婴儿中，CpG 3甲基化在NEC发生前很长时间为0.8%，在NEC发作前短时间增加到1.8%，在NEC发生后为2.0%（分别为P = 0.011；P = 0.021）。在CpG 1中也发现了类似模式，从75.4%增加到81.4%并保持在85.3%（分别为P = 0.027；P = 0.019）。对于此处未列出的其他基因，未发现这些变化。在NEC婴儿中存在此处未列出的其他基因的表观遗传变化，并且这些变化可能因NEC发作时间而异。此处未列出的其他基因的DNA甲基化差异可能会影响基因表达并增加患NEC的风险。本研究还证明了从粪便样本中提取人类DNA作为一种探索早产儿肠道的新型非侵入性方法，并且该方法也可用于坏死性小肠结肠炎患者。
