EV71型手足口病的肠道菌群结构特征分析

Analysis of the structural characteristics of intestinal flora in EV71 hand-foot-mouth disease

目的测定肠道病毒71型(EV71)型手足口病的肠道菌群结构并分析其特征。方法留取2020年1月—2021年12月经徐州医科大学附属宿迁医院确诊的EV71型手足口病及健康儿童粪便样本,提取DNA后行16S rDNA扩增子测序,并对测序后的生物信息进行分类、量化和对比。选用α多样性分析2组间的丰度、多样性差异;选用β多样性分析2组间的菌群结构差异;选用LDA分析和LEfSe分析比较2组间的显著差异菌属。结果共收集EV71型手足口病患儿(EV71组,45例)和健康儿童(对照组,35例)粪便标本80例。相对于对照组,EV71组肠道菌群多样性(shannon指数,P>0.05)和丰度(ace指数,P>0.05)变化差异无统计学意义,但其结构呈显著改变(weighted_unifrac,P<0.05),主要表现为奈瑟菌属(P<0.05)和克雷伯菌属(P<0.01)丰度升高,而罗姆布茨菌属(P<0.01)、小杆菌属(P<0.01)以及梭菌属(P<0.05)丰度降低。结论EV71型手足口病肠道菌群紊乱,以丁酸盐产生菌属丰度降低、机会致病菌属丰度升高为特征。该结果为后期EV71型手足口病的发病机制及微生态治疗提供了部分理论基础。

Objective To determine the structure and characteristics of intestinal flora in EV71 hand-foot-mouth disease.Methods Fecal samples were collected from healthy children and child patients with EV71 hand-foot-mouth disease who were diagnosed in Suqian Hospital Affiliated to Xuzhou Medical University from January 2020 to December 2021.After DNA extraction,16S rDNA amplicon sequencing was performed,and the obtained biological information was classified,quantified and compared.Alpha-diversity was used to analyze the differences in abundance and diversity between the two groups.Beta-diversity was used to analyze the differences in bacterial community structure between the two groups.LDA analysis and LEfSe analysis were used to compare the significantly different genera between the two groups.Results A total of 80 fecal samples were collected from children with EV71 hand-foot-mouth disease(the EV71 group,n=45)and healthy children(the control group,n=35).Compared with the control group,there were no significant changes in the diversity(shannon index,P>0.05)and abundance(ace index,P>0.05)of intestinal flora in the EV71 group.However,the structure of intestinal flora in EV71 group was significantly changed(weighted_unifrac,P<0.05),which was characterized in the increased abundance of Neisseria(P<0.05)and Klebsiella(P<0.01),and the deceased abundance of Romboutsia(P<0.01),Dialister(P<0.01)and Clostridium(P<0.05).Conclusions The intestinal flora of EV71 hand-foot-mouth disease is disordered,which is mainly characterized by the decrease of butyrate producing bacteria and the increase of opportunistic pathogenic bacteria.The results provide some theoretical evidence for the pathogenesis and microecological treatment of EV71 hand-foot-mouth disease in the advanced stage.