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Title: [Intestinal microbiome and its relationship with necrotizing enterocolitis in very low birth weight preterm infants].
Author: Wang C, Cui ML, Wang SN, Zhu XP.
Journal: Zhonghua Er Ke Za Zhi; 2022 Feb 02; 60(2):101-107. PubMed ID: 35090225.
Abstract:
Objective: To explore the composition of intestinal microflora prior to onset of necrotizing enterocolitis (NEC) in very low birth weight preterm infants. Methods: This was a multicenter prospective nested case-control study. A total of 46 very low birth weight preterm infants (birth weight <1 500 g and gestional age <35 weeks) within 24 h of life admitted into Neonatal Intensive Care Unit of Children's Hospital of Soochow University and Suzhou Municipal Hospital from April 20 to November 20, 2018 were enrolled. Baseline clinical data and fecal samples of these infants were collected. The subsequent sampling time points were 1st, 4th and 7th day in the first week of life then once per week consecutively. The endpoint of sampling was NEC occurrence, patient discharge or the 8th week post-discharge, whichever came first. Fecal samples were analyzed by 16 S rDNA high-throughput nucleotide sequencing. The control cases were infants without NEC who were matched to the NEC cases with a ratio of 1∶1. The operational taxonomic units (OTU), sequence number and shannon diversity index of the fecal samples were analyzed. Continuous variables were compared with t-test or non-parametric test, and χ² test or Fisher's exact test was used for categorical variables. Results: There were 23 patients in each group. The gestational age was (29.4±1.8) weeks in NEC group and (29.9±1.6) weeks in control group, including 13 males (57%) and 11 males (48%) in each group, respectively. Species abundance showed that the Firmicutes in both groups decreased temporarily at 7 days of age and then increased with age in control group, but not in NEC group, the Proteobacteria in both groups increased at 7 days of age and then decreased in control group, but kept increasing in NEC group. Regarding the other levels of taxonomy, compared with that of the control group, the NEC group had lower abundance of Proteobacteria, γ-proteobacteria and Enterobacteriaceae at 7 days of age, while higer abundance of Faecalibacterium at 14 days of age, meanwhile, lower Clostridium and Streptococcus at 21 days of age, lower Firmicutes, Clostridia and Clostridium perfringens and higher Proteobacteria and γ-proteobacteria at 28 days of age, these differences were all statistically significant (U=43.00, 43.00, 45.00, 80.00, 74.00, 76.00, 19.00, 8.00, 36.00, 25.00, 25.00,all P<0.05). The shannon index of NEC group was both lower than that of the controls at 21 days of age (2.4 (1.4, 3.0) vs. 3.1 (2.6, 4.0), U=67.00, P=0.027) and 28 days of age (2.4 (1.4, 2.8) vs. 3.9 (3.3, 4.2), U=12.00, P=0.001). Conclusions: The intestinal microflora profile of very low birth weight preterm infants has already changed prior to NEC development. The emergence of differential flora and the reduction of microflora diversity may facilitate early identification and prevention of NEC. 目的： 探讨早产极低出生体重儿（VLBWI）坏死性小肠结肠炎（NEC）发生前肠道菌群结构特征变化。 方法： 采用前瞻性巢式病例对照研究。将2018年4月20日至11月20日生后24 h内收住苏州大学附属儿童医院或苏州市立医院新生儿重症监护病房（NICU）且出生体重<1 500 g、出生胎龄<35周的46例早产VLBWI作为研究对象，采集所有早产VLBWI基本临床资料及粪便样本，粪便样本留取时间节点为生后1周内第1、4、7日龄，之后每周留取1次，留取终点为NEC发生或出院或生后第8周（以先到者为终点），粪便样本通过16 S rDNA高通量核苷酸测序。根据有无NEC发生分为NEC组和对照组，对照组按1∶1的比例匹配。分析2组粪便样本菌群的操作分类单元（OTU）组成、序列数及多样性shannon指数。采用t检验或非参数检验，χ²检验或Fisher确切概率法进行组间比较。 结果： NEC组23例，其中男13例（57%），出生胎龄（29.4±1.8）周；对照组23例，其中男11例（48%），出生胎龄（29.9±1.6）周。物种丰度差异分析显示，2组厚壁菌门在7日龄均有一过性下降，对照组随日龄增加有升高趋势，而NEC组无此趋势；2组变形菌门均于7日龄升高，对照组随日龄增加丰度逐渐减低，而NEC组持续增高；NEC组菌群与对照组比较，7日龄变形菌门、γ-变形菌纲、肠杆菌科丰度均低，14日龄粪杆菌属明显高，21日龄梭菌属、链球菌属均低，28日龄厚壁菌门、梭菌纲、产气荚膜梭菌均低，变形菌门、γ-变形菌纲均高，差异均有统计学意义（U=43.00、43.00、45.00、80.00、74.00、76.00、19.00、8.00、36.00、25.00、25.00，均P<0.05）。α多样性分析结果显示，NEC组shannon指数在21、28日龄均低于对照组［2.4（1.4，3.0）比3.1（2.6，4.0），2.4（1.4，2.8）比3.9（3.3，4.2），U=67.00、12.00，P=0.027、0.001］。 结论： 早产VLBWI在发展为NEC之前肠道菌群定植模式已改变，差异菌群的出现及菌群多样性的减低为早期识别和预防NEC发生提供可能。.

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