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脓毒症儿童的肠道菌群特征及益生菌的干预作用

Characteristics of gut microbiota in children with sepsis and influence of probiotic supplementation

摘要目的:分析脓毒症儿童肠道菌群特征及益生菌的干预作用。方法:采用前瞻性观察性研究方法,纳入收住我院儿童重症医学科(PICU)的脓毒症患儿34例随机分为两组,一组予以常规治疗(常规组,A组, n=17),另一组在常规治疗基础上添加益生菌辅助治疗(益生菌组,B组, n=17),同时选取健康儿童20例作为对照组(C组)。入组24 h内记录所有脓毒症患儿的一般情况及序贯器官衰竭评分(SOFA),并于入组后5~7 d,采集患儿的粪便样本,同期留取健康患儿粪便样本,运用高通量16S rRNA基因测序技术进行肠道菌群检测,进行生物信息学分析并预测肠道菌群功能,比较组间差异。 结果:α多样性指数及β多样性指数分析显示,两组脓毒症患儿肠道菌群的丰度均较健康儿童明显下降,同时菌群的个体差异也呈加大趋势,但是服用益生菌后,上述指标得到了显著改善( P<0.05);在菌门水平上,常规治疗组的拟杆菌门和放线菌门比例最低,变形菌门的数量明显增加( P<0.05);在菌属水平上,肠球菌成为常规治疗组中的优势菌种,而在益生菌组中双歧杆菌、普氏粪杆菌及丹毒丝菌、扭链胃球菌的比例明显提高( P<0.05);益生菌组与常规组相比,两者在线粒体合成、外泌体、mRNA转录降解及半胱氨酸代谢等通路的丰度存在明显差异。 结论:脓毒症儿童肠道菌群的多样性下降,结构稳定性差,同时拟杆菌减少伴变形杆菌增多,而添加益生菌辅助治疗后可增加患儿双歧杆菌及普氏粪杆菌等有益菌的比例,减少肠球菌等机会致病菌的数量,其差异性代谢通路可能与益生菌的作用机制相关。

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abstractsObjective:To investigate the characteristics of gut microbiota in children with sepsis and the effects of probiotic intervention.Methods:Thirty-four children with sepsis admitted to the Pediatric Intensive Care Unit of Henan Provincial People′s Hospital were enrolled in this prospective study from May 2019 to July 2020. They were randomly divided into two groups and received conventional treatment (conventional treatment group, n=17) and conventional treatment combined with probiotics (probiotics group, n=17), respectively. Twenty healthy children were selected as healthy control group. The baseline characteristics and sequential organ failure assessment (SOFA) score of all children with sepsis were recorded within 24 h after recruitment. Stool samples were collected 5-7 d after recruitment. High-throughput 16S rRNA gene sequencing was used to detect gut microbiota. Bioinformatic analysis and predictive functional profiling of microbial communities were performed to analyze the differences between groups. Results:The α-diversity and β-diversity indexes showed compared with the healthy control group, the two sepsis groups had lower abundance of gut microbiota, but greater individual differences in bacteria structure. These indexes were improved significantly following probiotic intervention ( P<0.05). At the level of phylum, the proportions of Bacteroidota and Actinobacteriota in the conventional treatment group were the lowest among the three groups, while the proportion of Proteobacteria increased significantly ( P<0.05). At the level of genus, Enterocoddus was the predominant bacterium in the conventional treatment group, while the abundance of Bifidobacterium, Faecalibacterium, Erysipelotrichaceae and Rumimococcus- torques in the probiotics group showed an upward trend ( P<0.05). Differences in the abundance of metabolic pathways, including mitochondrial synthesis, exosomes, mRNA transcription and degradation and cysteine metabolism, could be found between the two sepsis groups. Conclusions:This study revealed that children with sepsis exhibit a dysbiotic microbial community with reduced microbial diversity, declined structural stability, decreased abundance of Bacteroidota and enrichment of Proteobacteria. Probiotic supplementation could elevate the percentage of beneficial symbiotic bacteria and reduce the number of pathogenic bacteria. The differential metabolic pathways might be associated with the mechanism of probiotics in practice.

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DOI 10.3760/cma.j.cn112309-20201127-00533
发布时间 2021-06-30(万方平台首次上网日期,不代表论文的发表时间)
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