益生菌联合应用行为分析法治疗儿童孤独症谱系障碍的前瞻性随机对照研究

Effect of probiotics combined with applied behavior analysis in the treatment of children with autism spectrum disorder:a prospective randomized controlled trial

目的探讨益生菌联合应用行为分析法(applied behavioranalysis,ABA)治疗儿童孤独症谱系障碍(autism spectrumdisorder,ASD)的疗效。方法选取2019年5月至2020年12月在江苏大学附属医院就诊的ASD患儿41例,随机分为观察组(n=21)和对照组(n=20)。观察组给予口服益生菌联合ABA干预,对照组仅给予ABA干预,比较两组的疗效。在干预前、干预后3个月分别依据孤独症治疗评估量表(autism treatmentevaluation checklist,ATEC)对两组患儿行为症状的严重程度进行评分,并分别留取患儿的粪便标本,基于16s rRNA高通量测序分析两组患儿的肠道菌群差异。结果干预前,观察组与对照组ATEC评分差异无统计学意义(P>0.05);干预后3个月,观察组与对照组ATEC评分均较干预前明显下降,且观察组ATEC评分低于对照组(P<0.05)。干预前,观察组与对照组肠道菌群构成情况无明显差异;干预后3个月,观察组与对照组肠道菌群构成情况存在明显差异。观察组双歧杆菌属、乳杆菌属、粪杆菌属、瘤胃菌属、普雷沃菌属、布劳特菌属的相对丰度明显高于对照组(P<0.05),志贺氏菌属、梭状菌属的相对丰度明显低于对照组(P<0.05)。结论益生菌可能通过调节肠道菌群微生态进一步改善传统ABA治疗儿童ASD的疗效。

Objective To study the effect of probiotics combined with applied behavior analysis(ABA)in the treatment of children with autism spectrum disorder(ASD).Methods A total of 41 children with ASD who attended the Affiliated Hospital of Jiangsu University from May 2019 to December 2020 were enrolled and randomly divided into an observation group with 21 children and a control group with 20 children.The children in the observation group were given oral probiotics combined with ABA intervention,while those in the control group were given ABA intervention alone.The treatment outcomes were compared between the two groups.Autism Treatment Evaluation Checklist(ATEC)was used to evaluate the severity of behavioral symptoms in both groups before intervention and at 3 months after intervention.The fecal samples were collected to analyze the difference in intestinal flora between the two groups based on 16s rRNA high-throughput sequencing.Results Before intervention,there was no significant difference in the ATEC score between the observation and control groups(P>0.05).At 3 months after intervention,both groups had a significant reduction in the ATEC score,and the observation group had a significantly lower ATEC score than the control group(P<0.05).Before intervention,there was no significant difference in the composition of intestinal flora between the observation and control groups.At 3 months after intervention,there was a significant difference in the composition of intestinal flora between the observation and control groups.Compared with the control group,the observation group had significantly higher relative abundances of Bifidobacterium,Lactobacillus,Coprobacillus,Ruminococcus,Prevotella,and Blautia(P<0.05)and significantly lower relative abundances of Shigella and Clostridium(P<0.05).Conclusions Probiotics may improve the effect of conventional ABA intervention in children with ASD by regulating intestinal flora.