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

李玉勤; 孙映红; 梁亚鹏; 周凡; 杨洁; 金胜利

doi:10.7499/j.issn.1008-8830.2108085

PDF(756 KB)

HTML

中国当代儿科杂志 ›› 2021, Vol. 23 ›› Issue (11) : 1103-1110. DOI: 10.7499/j.issn.1008-8830.2108085

论著·临床研究

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

李玉勤¹, 孙映红¹, 梁亚鹏², 周凡¹, 杨洁¹, 金胜利¹

作者信息 +

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

LI Yu-Qin, SUN Ying-Hong, LIANG Ya-Peng, ZHOU Fan, YANG Jie, JIN Sheng-Li

Author information +

文章历史 +

摘要

目的探讨益生菌联合应用行为分析法（applied behavior analysis，ABA）治疗儿童孤独症谱系障碍（autism spectrum disorder，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 treatment evaluation 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。引用格式:

Abstract

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. Citation:

导出引用

李玉勤, 孙映红, 梁亚鹏, 周凡, 杨洁, 金胜利. 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[J]. 中国当代儿科杂志. 2021, 23(11): 1103-1110 https://doi.org/10.7499/j.issn.1008-8830.2108085

LI Yu-Qin, SUN Ying-Hong, LIANG Ya-Peng, ZHOU Fan, YANG Jie, JIN Sheng-Li. Effect of probiotics combined with applied behavior analysis in the treatment of children with autism spectrum disorder: a prospective randomized controlled trial[J]. Chinese Journal of Contemporary Pediatrics. 2021, 23(11): 1103-1110 https://doi.org/10.7499/j.issn.1008-8830.2108085

参考文献

1 唐婷, 朱江, 郭敏, 等. 孤独症谱系障碍儿童便秘及睡眠问题与情绪行为问题的关系[J]. 重庆医科大学学报, 2020, 45(1): 85-90. DOI: 10.13406/j.cnki.cyxb.001940.
2 Baio J, Wiggins L, Christensen DL, et al. Prevalence of autism spectrum disorder among children aged 8 years—autism and developmental disabilities monitoring network, 11 sites, United States, 2014[J]. MMWR Surveill Summ, 2018, 67(6): 1-23. PMID: 29701730. PMCID: PMC5919599. DOI: 10.15585/mmwr.ss6706a1.
3 中华医学会儿科学分会发育行为学组, 中国医师协会儿科分会儿童保健专业委员会, 儿童孤独症诊断与防治技术和标准研究项目专家组. 孤独症谱系障碍患儿常见共患问题的识别与处理原则[J]. 中华儿科杂志, 2018, 56(3): 174-178. PMID: 29518826. DOI: 10.3760/cma.j.issn.0578-1310.2018.03.004.
4 Roane HS, Fisher WW, Carr JE. Applied behavior analysis as treatment for autism spectrum disorder[J]. J Pediatr, 2016, 175: 27-32. PMID: 27179552. DOI: 10.1016/j.jpeds.2016.04.023.
5 李珂, 江晓东, 季忆婷, 等. 孤独症谱系障碍儿童胃肠问题检出情况初探[J]. 上海交通大学学报(医学版), 2017, 37(11): 1506-1511. DOI: 10.3969/j.issn.1674-8115.2017.11.010.
6 Ding HT, Taur Y, Walkup JT. Gut microbiota and autism: key concepts and findings[J]. J Autism Dev Disord, 2017, 47(2): 480-489. PMID: 27882443. DOI: 10.1007/s10803-016-2960-9.
7 李玉勤, 孙映红, 梁亚鹏, 等. 孤独谱系障碍患儿消化道症状与行为表现关系分析[J]. 中国儿童保健杂志, 2020, 28(11): 1259-1262. DOI: 10.11852/zgetbjzz2020-0412.
8 Regier DA, Kuhl EA, Kupfer DJ. The DSM-5: classification and criteria changes[J]. World Psychiatry, 2013, 12(2): 92-98. PMID: 23737408. PMCID: PMC3683251. DOI: 10.1002/wps.20050.
9 Mahapatra S, Khokhlovich E, Martinez S, et al. Longitudinal epidemiological study of autism subgroups using Autism Treatment Evaluation Checklist (ATEC) score[J]. J Autism Dev Disord, 2020, 50(5): 1497-1508. PMID: 30062397. PMCID: PMC7211200. DOI: 10.1007/s10803-018-3699-2.
10 Stanislaw H, Howard J, Martin C. Helping parents choose treatments for young children with autism: a comparison of applied behavior analysis and eclectic treatments[J]. J Am Assoc Nurse Pract, 2020, 32(8): 571-578. PMID: 31738275. DOI: 10.1097/JXX.0000000000000290.
11 Yu Q, Li EY, Li LG, et al. Efficacy of interventions based on applied behavior analysis for autism spectrum disorder: a meta-analysis[J]. Psychiatry Investig, 2020, 17(5): 432-443. PMID: 32375461. PMCID: PMC7265021. DOI: 10.30773/pi.2019.0229.
12 Al Backer NB. Correlation between Autism Treatment Evaluation Checklist (ATEC) and Childhood Autism Rating Scale (CARS) in the evaluation of autism spectrum disorder[J]. Sudan J Paediatr, 2016, 16(1): 17-22. PMID: 27651549. PMCID: PMC5025928.
13 方慧, 任艳玲, 李春燕, 等. 孤独症治疗评定量表中文版的信度和效度检验[J]. 四川精神卫生, 2019, 32(6): 518-522. DOI: 10.11886/scjsws20190902002.
14 朱江, 郭敏, 杨亭, 等. 孤独症谱系障碍患儿胃肠道症状与行为表现关系研究[J]. 中华儿科杂志, 2017, 55(12): 905-910. PMID: 29262469. DOI: 10.3760/cma.j.issn.0578-1310.2017.12.007.
15 Schrenzel J, Lazarevic V. Intestinal microbiota: towards therapeutic applications[J]. Rev Med Suisse, 2017, 13(582): 1959-1961. PMID: 29120545.
16 Pulikkan J, Maji A, Dhakan DB, et al. Gut microbial dysbiosis in Indian children with autism spectrum disorders[J]. Microb Ecol, 2018, 76(4): 1102-1114. PMID: 29564487. DOI: 10.1007/s00248-018-1176-2.
17 Averina OV, Danilenko VN. Human intestinal microbiota: role in development and functioning of the nervous system[J]. Mikrobiologiia, 2017, 86(1): 5-24. PMID: 30207138.
18 赵英欣, 张旭静, 郑毅. 肠道微生物-大脑轴与孤独症谱系障碍[J]. 中华精神科杂志, 2019, 52(3): 224-227. DOI: 10.3760/cma.j.issn.1006-7884.2019.03.010.
19 Strati F, Cavalieri D, Albanese D, et al. New evidences on the altered gut microbiota in autism spectrum disorders[J]. Microbiome, 2017, 5(1): 24. PMID: 28222761. PMCID: PMC5320696. DOI: 10.1186/s40168-017-0242-1.
20 Grimaldi R, Gibson GR, Vulevic J, et al. A prebiotic intervention study in children with autism spectrum disorders (ASDs)[J]. Microbiome, 2018, 6(1): 133. PMID: 30071894. PMCID: PMC6091020. DOI: 10.1186/s40168-018-0523-3.
21 Ferguson BJ, Marler S, Altstein LL, et al. Psychophysiological associations with gastrointestinal symptomatology in autism spectrum disorder[J]. Autism Res, 2017, 10(2): 276-288. PMID: 27321113. PMCID: PMC5526214. DOI: 10.1002/aur.1646.
22 赵锐豪, 郑鹏远, 刘思濛, 等. 孤独症谱系障碍儿童肠道菌群与行为症状的相关研究[J]. 中国当代儿科杂志, 2019, 21(7): 663-669. PMID: 31315765. PMCID: PMC7389106. DOI: 10.7499/j.issn.1008-8830.2019.07.009.
23 吴薇岚, 江蕙芸, 陈雪, 等. 孤独症谱系障碍儿童肠道菌群多样性的研究[J]. 中国儿童保健杂志, 2020, 28(9): 980-984. DOI: 10.11852/zgetbjzz2019-1045.
24 Adams JB, Borody TJ, Kang DW, et al. Microbiota transplant therapy and autism: lessons for the clinic[J]. Expert Rev Gastroenterol Hepatol, 2019, 13(11): 1033-1037. PMID: 31665947. DOI: 10.1080/17474124.2019.1687293.
25 Fung TC, Olson CA, Hsiao EY. Interactions between the microbiota, immune and nervous systems in health and disease[J]. Nat Neurosci, 2017, 20(2): 145-155. PMID: 28092661. PMCID: PMC6960010. DOI: 10.1038/nn.4476.
26 Sgritta M, Dooling SW, Buffington SA, et al. Mechanisms underlying microbial-mediated changes in social behavior in mouse models of autism spectrum disorder[J]. Neuron, 2019, 101(2): 246-259.e6. PMID: 30522820. PMCID: PMC6645363. DOI: 10.1016/j.neuron.2018.11.018.
27 Maqsood R, Stone TW. The gut-brain axis, BDNF, NMDA and CNS disorders[J]. Neurochem Res, 2016, 41(11): 2819-2835. PMID: 27553784. DOI: 10.1007/s11064-016-2039-1.
28 Lammert CR, Frost EL, Bolte AC, et al. Cutting edge: critical roles for microbiota-mediated regulation of the immune system in a prenatal immune activation model of autism[J]. J Immunol, 2018, 201(3): 845-850. PMID: 29967099. PMCID: PMC6057827. DOI: 10.4049/jimmunol.1701755.
29 Port RG, Gaetz W, Bloy L, et al. Exploring the relationship between cortical GABA concentrations, auditory gamma-band responses and development in ASD: evidence for an altered maturational trajectory in ASD[J]. Autism Res, 2017, 10(4): 593-607. PMID: 27696740. PMCID: PMC5376374. DOI: 10.1002/aur.1686.
30 Lee E, Kim BJ, Kang MJ, et al. Dynamics of gut microbiota according to the delivery mode in healthy Korean infants[J]. Allergy Asthma Immunol Res, 2016, 8(5): 471-477. PMID: 27334787. PMCID: PMC4921703. DOI: 10.4168/aair.2016.8.5.471.
31 吴晓丽, 梁姗, 王涛, 等. 肠道微生物与自闭症研究进展[J]. 科学通报, 2018, 63(18): 1803-1821. DOI: 10.1360/N972017-01186.
32 Robertson CE, Ratai EM, Kanwisher N. Reduced GABAergic action in the autistic brain[J]. Curr Biol, 2016, 26(1): 80-85. PMID: 26711497. DOI: 10.1016/j.cub.2015.11.019.
33 Pequegnat B, Sagermann M, Valliani M, et al. A vaccine and diagnostic target for Clostridium bolteae, an autism-associated bacterium[J]. Vaccine, 2013, 31(26): 2787-2790. PMID: 23602537. DOI: 10.1016/j.vaccine.2013.04.018.
34 Lobzhanidze G, Japaridze N, Lordkipanidze T, et al. Behavioural and brain ultrastructural changes following the systemic administration of propionic acid in adolescent male rats. Further development of a rodent model of autism[J]. Int J Dev Neurosci, 2020, 80(2): 139-156. PMID: 31997401. DOI: 10.1002/jdn.10011.
35 Careaga M, Rogers S, Hansen RL, et al. Immune endophenotypes in children with autism spectrum disorder[J]. Biol Psychiatry, 2017, 81(5): 434-441. PMID: 26493496. PMCID: PMC4788581. DOI: 10.1016/j.biopsych.2015.08.036.
36 Estes ML, McAllister AK. Brain, immunity, gut: "BIG" links between pregnancy and autism[J]. Immunity, 2017, 47(5): 816-819. PMID: 29166585. DOI: 10.1016/j.immuni.2017.10.019.