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发育医学电子杂志  2026, Vol. 14 Issue (1): 28-37    
  论著 |
胃肠外营养相关性胆汁淤积症早产儿肠道菌群特征的研究
关函洲  冀俊毅   张涛   高歌  张新华
1. 山西省儿童医院 新生儿内科,山西 太原 030013;2. 山西省儿童医院 检验科,山西 太原 030013;3. 山西医科大学 人文社会科学学院,山西 太原 030001
Study on the characteristics of intestinal flora in premature infants with parenteral nutrition- associated cholestasis
Guan Hanzhou , Ji Junyi , Zhang Tao,et al.
(1. Department of Neonatology, Shanxi Provincial Children Hospital, Shanxi, Taiyuan 030013, China; 2. Department of Laboratory, Shanxi Provincial Children Hospital, Shanxi, Taiyuan 030013, China; 3. School of Humanities and Social Sciences, Shanxi Medical University, Shanxi, Taiyuan 030001, China
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摘要 
【摘要】 目的  通过 16S 核糖体核糖核酸(16S ribosomal RNA,16S rRNA)高通量基因测序分析胃肠外
营养相关性胆汁淤积症(parenteral nutrition-associated cholestasis,PNAC)早产儿肠道菌群变化的特征。
方法 采用前瞻性、纵向、单中心队列研究方法,收集 2022 年 1 月至 8 月就诊于山西省儿童医院新生儿
内科的20例早产儿的临床资料,其中PNAC组15例,于治疗前后共留取粪便标本30份,标记为P1组(治
疗前,日龄≤ 28 d,n=15)与 P2 组(治疗后,日龄 >29 d,n=15);非 PNAC 组早产儿 5 例,分别于同时间点留取标本共 10 份作为对照,标记为 C1 组(日龄≤ 28 d,n=5)与 C2 组(日龄 >29 d,n=5)。分析临床资料及肝胆生化指标,并对粪便标本的 DNA 进行测序及生物信息学分析。统计学方法采用独立样本 t 检验、χ 2 检验或 Fisher 确切概率法。 结果  PNAC 组和非 PNAC 组早产儿的一般资料比较,差异均无统
计学意义(P 值均 >0.05),且预后均良好。线性判别分析效应大小(linear discriminant analysis effect size,LEfSe)结果显示了各组富集的细菌:C1 组的厚壁菌门和梭菌属,C2 组的梭状芽孢杆菌属,P1 组的变形菌门和未分类大肠杆菌属,P2 组的拟杆菌门和考拉杆菌属。利用 Metastats 分析行组间 t 检验发现,与
C1 组比较,P1 组有害菌丰度增加,有益菌及机会致病菌丰度减少。与 C2 组相比,P2 组有益菌丰度仍低,
有害菌丰度仍高。4 组样本肠道菌群丰度、均匀性、多样性由低到高依次为:P1 组、C2 组、C1 组、P2 组。α 多样性比较结果显示,C1 组与 P1 组早产儿粪便菌群丰度的覆盖估计值(abundance-based coverage
estimator,ACE)指数、Chao1 指数和 Shannon 指数的差异有统计学意义(P 值均 <0.05)。β 多样性比
较结果显示,主坐标分析(principal coordinates analysis,PCoA)表明,4 组样本的菌群结构存在显著差异
(R2 =0.136,P=0.006);运用 PERMANOVA 分析进行组间差异检验,结果显示,仅 C1 组与 P1 组(R2 =0.146,P=0.004)菌群结构存在显著差异。 结论 PNAC 早产儿治疗前后肠道菌群有明显变化,未治疗时肠道菌群丰度、均匀性、多样性降低,肠道有害菌增加,有益菌属减少;经积极治疗后的 PNAC 早产儿肠道菌群逐渐恢复正常且预后较好。非 PNAC 组早产儿未使用益生菌,随日龄增长肠道菌群多样性无变化。
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关键词:  胃肠外营养  胆汁淤积症  早产儿  胃肠道微生物组  16S 核糖体核糖核酸    
Abstract: 【Abstract】 Objective To analyze the characteristics of the intestinal flora in premature infants with 
parenteral nutrition-associated cholestasis (PNAC) by high-throughput 16S ribosomal RNA (16S rRNA)
sequencing. Methods Using a prospective, longitudinal, single-center cohort study method, the clinical
data of 20 premature infants admitted to the Department of Neonatology, Shanxi Provincial Children
Hospital from January to August 2022 were collected. Among them, 15 premature infants in the PNAC
group were sampled for fecal specimens before and after treatment, which were labeled as P1 group
(before treatment, age≤28 d, n=15) and P2 group (after treatment, age>29 d, n=15); the non-PNAC group consisted of 5 premature infants who were sampled at the same time points, and their fecal specimens were labeled as C1 group (age≤28 d, n=5) and C2 group (age>29 d, n=5). The clinical data and liver-biliary biochemical indicators were analyzed, and conducted sequencing and bioinformatics analysis on the DNA of the fecal specimens. Statistical methods were performed by t-test, χ 2 -test and Fisher exact probability method. Results There was no significant difference in general conditions between the PNAC group and the non-PNAC group (all P>0.05), and both groups had good prognosis. The results of linear discriminant analysis effect size (LEfSe) showed the most abundant bacteria in each group: C1 group of Firmicutes and Clostridiaceae, C2 group of Bacillus cereus group, P1 group of Proteobacteria and unclassified Escherichia coli, and P2 group of Bacteroidetes and Corynebacteriaceae. Using Metastats analysis for group-wise t-test, it was found that the abundance of harmful bacteria increased in P1 group compared with C1 group, while theabundance of beneficial bacteria and opportunistic pathogens decreased. The abundance of beneficial bacteria was still low in P2 group compared with C2 group, and the abundance of harmful bacteria was still high. The order of intestinal flora community abundance, uniformity, and diversity in the four samples was P1 group, C2 group, C1 group, and P2 group. The results of the alpha diversity comparison showed that there were statistically significant differences in the abundance-based coverage estimator (ACE) index, Chao1 index, and Shannon index of fecal microbiota abundance between group C1 and group P1(all P<0.05). The results of the beta diversity comparison showed that the principal coordinates analysis (PCoA) indicated that there were significant differences in the microbial community structure among the four groups (R2 =0.136, P=0.006). Using PERMANOVA analysis for intergroup difference testing, the results showed that only the C1 group and P1 group had significant differences in microbial community structure (R2 =0.146, P=0.004). Conclusion There are significant changes in the intestinal flora of PNAC premature infants before and after treatment. In
untreated premature infants with PNAC, the abundance, uniformity and diversity of intestinal flora decreased, the harmful bacteria increased, and the beneficial bacteria decreased. After treatment, the intestinal flora of preterm infants with PNAC gradually returned to normal, and the prognosis was good. Premature infants in the non-PNAC group did not receive probiotics, and there was no change in intestinal flora diversity as their age increased.
Key words:  Parenteral nutrition    Cholestasis    Infant, premature    Gastrointestinal microbiome    16S ribosomal RNA
收稿日期:  2024-07-19                     发布日期:  2026-02-05     
基金资助: 
国家临床重点专科建设项目 (晋卫办医函〔2023〕9 号);山西省儿童医院院级课题(2021018)
通讯作者:  张新华    E-mail:  张新华(Email:13835107719@qq.com)
引用本文:    
关函洲 冀俊毅 张涛 高歌 张新华.
胃肠外营养相关性胆汁淤积症早产儿肠道菌群特征的研究
[J]. 发育医学电子杂志, 2026, 14(1): 28-37.
Guan Hanzhou , Ji Junyi , Zhang Tao, et al..
Study on the characteristics of intestinal flora in premature infants with parenteral nutrition- associated cholestasis
. Journal of Developmental Medicine(Electronic Version), 2026, 14(1): 28-37.
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