Dysbiosis anticipating necrotizing enterocolitis in very premature infants.

Dysbiosis anticipating necrotizing enterocolitis in very premature infants.
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早产儿的生态失调预示着坏死性小肠结肠炎。

DOI:
10.1093/cid/ciu822
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发表时间:
2015-02-01
期刊:
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子:
--
通讯作者:
Kroll JS
Kroll JS
中科院分区:
其他
文献类型:
--
作者:
Sim K;Shaw AG;Randell P;Cox MJ;McClure ZE;Li MS;Haddad M;Langford PR;Cookson WO;Moffatt MF;Kroll JS

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使用16 S rRNA基因测序和靶向培养,我们比较了坏死性小肠结肠炎(NEC)婴儿和对照婴儿粪便样本中的微生物群。两个显著特征与NEC相关:1个与优势产气荚膜梭菌相关,1个与优势肠杆菌科相关。背景:坏死性小肠结肠炎(NEC)是早产儿的一种毁灭性炎症性肠病,推测与感染有关。 疑似NEC可能与败血症难以区分,在确诊病例中,婴儿可能在诊断后数小时内死亡。目前的治疗是支持性的。目前迫切需要一种症状前诊断的方法。我们的目的是确定早产儿NEC诊断前胃肠道微生物群中的微生物特征。方法:从369名早产儿的2年队列中收集粪便样本和临床资料。 下一代16 S核糖体RNA基因区测序用于表征12例NEC新生儿、8例疑似NEC新生儿和44例对照新生儿的诊断前粪便样本的微生物群。使用逻辑回归来确定临床特征和区分病例与对照的操作分类单位(OTU)。培养样品,并使用基质辅助激光解吸/电离-飞行时间鉴定分离株。梭菌分离株进行分型和毒素基因检测。结果:确诊NEC的婴儿的诊断前样本中,梭菌OTU过多(P = 0.006)。 培养证实存在A型产气荚膜梭菌。荧光扩增片段长度多态性分型确定没有分离株是相同的。来自不携带大量C的NEC婴儿的诊断前样本。产气荚膜杆菌显示过量的克雷伯氏菌OTU(P = 0.049)。长期持续气道正压通气(CPAP)治疗和补充氧气也与NEC风险增加有关。结论:两种粪便微生物群特征(梭菌属和克雷伯氏菌属OTU)和需要延长CPAP氧信号增加了症状前婴儿NEC的风险。 这些生物标志物将有助于开发一种筛查工具,以实现NEC的早期诊断。临床试验注册NCT 01102738。 
Using 16S rRNA gene sequencing and targeted culture, we compared microbiota in fecal samples from infants with necrotizing enterocolitis (NEC) and controls. Two significant signatures were associated with NEC: 1 with dominant Clostridium perfringens and 1 with dominant Enterobacteriaceae. Background. Necrotizing enterocolitis (NEC) is a devastating inflammatory bowel disease of premature infants speculatively associated with infection. Suspected NEC can be indistinguishable from sepsis, and in established cases an infant may die within hours of diagnosis. Present treatment is supportive. A means of presymptomatic diagnosis is urgently needed. We aimed to identify microbial signatures in the gastrointestinal microbiota preceding NEC diagnosis in premature infants. Methods. Fecal samples and clinical data were collected from a 2-year cohort of 369 premature neonates. Next-generation sequencing of 16S ribosomal RNA gene regions was used to characterize the microbiota of prediagnosis fecal samples from 12 neonates with NEC, 8 with suspected NEC, and 44 controls. Logistic regression was used to determine clinical characteristics and operational taxonomic units (OTUs) discriminating cases from controls. Samples were cultured and isolates identified using matrix-assisted laser desorption/ionization–time of flight. Clostridial isolates were typed and toxin genes detected. Results. A clostridial OTU was overabundant in prediagnosis samples from infants with established NEC (P = .006). Culture confirmed the presence of Clostridium perfringens type A. Fluorescent amplified fragment-length polymorphism typing established that no isolates were identical. Prediagnosis samples from NEC infants not carrying profuse C. perfringens revealed an overabundance of a Klebsiella OTU (P = .049). Prolonged continuous positive airway pressure (CPAP) therapy with supplemental oxygen was also associated with increased NEC risk. Conclusions. Two fecal microbiota signatures (Clostridium and Klebsiella OTUs) and need for prolonged CPAP oxygen signal increased risk of NEC in presymptomatic infants. These biomarkers will assist development of a screening tool to allow very early diagnosis of NEC. Clinical Trials Registration. NCT01102738.
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