基于16S rDNA高通量测序技术对克罗恩病患儿肠道菌群变化的研究

Intestinal flora imbalance in children with Crohn′s disease based on 16S rDNA high-throughput sequencing

目的研究克罗恩病(Crohn′s disease, CD)儿童和正常人群肠道菌群的分布,寻找与CD发生发展显著相关的菌属结构。方法纳入CD患儿36例和健康儿童21例,CD患儿分为活动期22例、缓解期14例,采用16S rDNA高通量测序技术,分析各组肠道菌群的生物多样性与结构组成。结果 CD组患儿(活动期与缓解期)肠道菌群丰富度指数、香浓多样性指数较健康儿童组有明显下降,差异有统计学意义(F=8.829 0,P=0.001 0,P=0.004 5;F=8.890 0,P=0.000 3,P=0.035 6)。在门类水平,所有CD患儿肠道菌群的放线菌门数量减少,变形菌门数量增多。在菌属水平,与健康儿童组相比,所有CD组患儿Faecalibacterium相对丰度显著减低,Klebsiella(克雷伯菌属)、Enterococcus(肠球菌属)相对丰度显著升高。活动期CD组Blautia(布劳特菌属)、Bifidobacterium(双歧杆菌属)、Subdoligranulum、Lachnospira(毛螺旋菌属)、Anaerostipes(丁酸弧菌属)、Eubacteriumrectalegroup(直肠杆菌属)的相对丰度明显下降。结论 CD患儿肠道菌群结构及相对丰度较健康儿童存在显著差异。肠道菌群结构的异常与儿童CD的发生发展存在相关性。

Objective To identify the dysbacteriosis in pediatric patients with Crohn′s disease(CD) and find out the special gut bacteria related to CD. Methods Thirty-six children with CD and twenty-one healthy children were included and divided into active CD group, remission CD group or healthy control group. The 16 S rDNA high-throughput sequencing technology was used to detect the changes in gut microbiota composition and abundance. Results The Chao1 indexes and Shannon indexes in CD groups(active and remission stage) were significantly lower than those in healthy control group, respectively(F=8.829 0, P=0.001 0, P=0.004 5;F=8.890 0, P=0.000 3, P=0.035 6). At the level of phylum, the relative abundance of Actinobacteria decreased while that of Proteobacteria increased in CD groups, compared with healthy control group. At the level of genus, the relative abundance of Faecalibacterium decreased while Klebsiella and Enterococcus increased in CD groups, compared with healthy control group. The relative abundance of Blautia, Bifidobacterium, Subdoligranulum, Lachnospira, Anaerostipes and Eubacterium;ectale;roup decreased in active CD group, compared with the other two groups. Conclusion There is a correlation between the abnormal changes of intestinal flora structure and the occurrence and development of pediatric CD.