孤独症谱系障碍微生物-肠-脑轴研究进展

凌梅; 汪月红; 李娜; 熊玉红; 杨舒; 徐桂凤

doi:10.11852/zgetbjzz2024-1431

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中国儿童保健杂志 ›› 2025, Vol. 33 ›› Issue (7) : 778-782. DOI: 10.11852/zgetbjzz2024-1431

综述

孤独症谱系障碍微生物-肠-脑轴研究进展

凌梅¹, 汪月红², 李娜¹, 熊玉红², 杨舒¹, 徐桂凤^1,2

作者信息 +

Research progress of the microbiota-gut-brain axis in autism spectrum disorder and treatment

LING Mei¹, WANG Yuehong², LI Na¹, XIONG Yuhong², YANG Shu¹, XU Guifeng^1,2

Author information +

文章历史 +

摘要

孤独症谱系障碍(ASD)是一种复杂的神经系统发育障碍性疾病,近20年来其患病率呈持续增长趋势。ASD患者的行为表现可能与微生物-肠-脑轴(BGM轴)存在双向调节机制,而BGM轴中肠道微生物群改变已有很多报道。因此,本文总结了不同剂量和疗程的益生菌、益生元、合生元和粪便微生物群移植治疗ASD的效果,ASD治疗评估量表(ATEC)、儿童孤独症评定量表(CARS)、ASD患者异常行为检查量表-日本版(ABC-J)等评估指标显示干预后ASD患者症状均有改善,但4种疗法仍有缺少大样本临床数据的不足,以及针对ASD患者异质性的个性化剂量和疗程调整不充分的短板。未来仍需要对这些针对微生物群的干预措施的有效性和优化方案进一步研究。

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, and its prevalence has shown a sustained upward trend over the past two decades.Emerging evidence suggests a bidirectional regulatory mechanism between ASD-related behavioral manifestations and the microbiota-gut-brain axis (MGB axis), with numerous studies reporting alterations in gut microbiota composition within this axis.This article reviews the therapeutic effects of probiotics, prebiotics, synbiotics, and fecal microbiota transplantation on ASD at varying dosages and treatment durations.Post-intervention assessments using standardized scales, including the Autism Treatment Evaluation Checklist (ATEC), Childhood Autism Rating Scale (CARS), and Autism Behavior Checklist-Japanese Version (ABC-J), demonstrated symptomatic improvements in individuals with ASD.However, all four interventions share limitations, such as a lack of large-scale clinical data and inadequate personalization of dosage and treatment duration to address the heterogeneity of ASD patients.Future research is warranted to validate the efficacy of these microbiota-targeted interventions and optimize treatment protocols for broader clinical application.

导出引用

凌梅, 汪月红, 李娜, 熊玉红, 杨舒, 徐桂凤. 孤独症谱系障碍微生物-肠-脑轴研究进展[J]. 中国儿童保健杂志. 2025, 33(7): 778-782 https://doi.org/10.11852/zgetbjzz2024-1431

LING Mei, WANG Yuehong, LI Na, XIONG Yuhong, YANG Shu, XU Guifeng. Research progress of the microbiota-gut-brain axis in autism spectrum disorder and treatment[J]. Chinese Journal of Child Health Care. 2025, 33(7): 778-782 https://doi.org/10.11852/zgetbjzz2024-1431

中图分类号： R749.94

参考文献

[1] Lord C, Brugha TS, Charman T, et al.Autism spectrum disorder[J].Nat Rev Dis Primers, 2020, 6(1): 5.
[2] First MB, Clarke DE, Yousif L, et al.DSM-5-TR: Rationale, process, and overview of changes[J].Psychiatr Serv, 2023, 74(8): 869-875.
[3] Maenner MJ, Warren Z, Williams AR, et al.Prevalence and characteristics of autism spectrum disorder among children aged 8 years: Autism and developmental disabilities monitoring network, 11 Sites, United States, 2020[J].MMWR Surveill Summ, 2023, 72(2): 1-14.
[4] Zeidan J, Fombonne E, Scorah J, et al.Global prevalence of autism: A systematic review update[J].Autism Res, 2022, 15(5): 778-790.
[5] Khachadourian V, Mahjani B, Sandin S, et al.Comorbidities in autism spectrum disorder and their etiologies[J].Transl Psychiatry, 2023, 13(1): 71.
[6] Al-Beltagi M.Autism medical comorbidities[J].World J Clin Pediatr, 2021, 10(3): 15-28.
[7] Chakraborty P, Carpenter KLH, Major S, et al.Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders[J].Autism, 2021, 25(2): 405-415.
[8] Bjørklund G, Pivina L, Dadar M, et al.Gastrointestinal alterations in autism spectrum disorder: What do we know?[J].Neurosci Biobehav Rev, 2020, 118: 111-120.
[9] Nalbant K, Erden S, Yazar A, et al.Investigation of the relation between epithelial barrier function and autism symptom severity in children with autism spectrum disorder[J].J Mol Neurosci, 2022, 72(4): 741-747.
[10] Kara H, Burak Açıkel S, Çetinkaya M, et al.Serum zonulin levels are higher among children with autism spectrum disorders and correlated with social impairment[J].Alpha Psychiatry, 2021, 22(5): 250-256.
[11] Azouz HG, Zakaria NHE, Khalil AF, et al.Gastrointestinal manifestations and their relation to faecal calprotectin in children with autism[J].Prz Gastroenterol, 2021, 16(4): 352-357.
[12] Korteniemi J, Karlsson L, Aatsinki A.Systematic review: Autism spectrum disorder and the gut microbiota[J].Acta Psychiat Scand, 2023, 148(3): 242-254.
[13] Vernocchi P, Ristori MV, Guerrera S, et al.Gut microbiota ecology and inferred functions in children with ASD compared to neurotypical subjects[J].Front Microbiol, 2022, 13: 871086.
[14] Han Y, Xiong W, Liu J, et al.Associations of serum cytokine levels and interleukin-6-572C/G polymorphism with myelin damage in Chinese children with autism spectrum disorder[J].Neuroscience, 2021, 465: 95-104.
[15] Yildirim V, Simsek S, Cetin I, et al.Kynurenine, kynurenic acid, quinolinic acid and interleukin-6 levels in the serum of patients with autism spectrum disorder[J].Medicina (Kaunas, Lithuania), 2023, 59(11): 1906.
[16] Cao X, Liu K, Liu J, et al.Dysbiotic gut microbiota and dysregulation of cytokine profile in children and teens with autism spectrum disorder[J].Front Neurosci, 2021, 15: 635925.
[17] Shim S, Ha S, Choi J, et al.Alterations in plasma cytokine levels in Korean children with autism spectrum disorder[J].Yonsei Med J, 2024, 65(2): 70-77.
[18] Bridi MCD, Peixoto L.Excitatory/Inhibitory imbalance as a mechanism linking autism and sleep problems[J].Curr Opin Neurobiol, 2025, 90: 102968.
[19] Wang Q, Yang Q, Liu X.The microbiota-gut-brain axis and neurodevelopmental disorders[J].Protein Cell, 2023, 14(10): 762-775.
[20] Socała K, Doboszewska U, Szopa A, et al.The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders[J].Pharmacol Res, 2021, 172: 105840.
[21] Dan Z, Mao X, Liu Q, et al.Altered gut microbial profile is associated with abnormal metabolism activity of autism spectrum disorder[J].Gut Microbes, 2020, 11(5): 1246-1267.
[22] Kasarello K, Cudnoch-Jedrzejewska A, Czarzasta K.Communication of gut microbiota and brain via immune and neuroendocrine signaling[J].Front Microbiol, 2023, 14: 1118529.
[23] Hill C, Guarner F, Reid G, et al.Expert consensus document.The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic[J].Nat Rev Gastroenterol Hepatol, 2014, 11(8): 506-514.
[24] Mazzone L, Dooling SW, Volpe E, et al.Precision microbial intervention improves social behavior but not autism severity: A pilot double-blind randomized placebo-controlled trial[J].Cell Host Microbe, 2024, 32(1): 106-116.e6.
[25] Schmitt LM, Smith EG, Pedapati EV, et al.Results of a phase Ib study of SB-121, an investigational probiotic formulation, a randomized controlled trial in participants with autism spectrum disorder[J].Sci Rep, 2023, 13(1): 5192.
[26] 李玉勤, 孙映红, 梁亚鹏, 等.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.
Li YQ, Sun YH, Liang YP, et al.Effect of probiotics combined with applied behavior analysis in the treatment of children with autism spectrum disorder:A prospective randomized controlled trial[J].Chin J Contemp Pediatr, 2021, 23(11): 1103-1110.(in Chinese)
[27] Bojović K, Ignjatović DI, Soković Bajić S, et al.Gut microbiota dysbiosis associated with altered production of short chain fatty acids in children with neurodevelopmental disorders[J].Front Cell Infect Microbiol, 2020, 10: 223.
[28] He X, Liu W, Tang F, et al.Effects of probiotics on autism spectrum disorder in children: A systematic review and meta-analysis of clinical trials[J].Nutrients, 2023, 15(6):1415.
[29] Gibson GR, Hutkins R, Sanders ME, et al.Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics[J].Nat Rev Gastroenterol Hepatol, 2017, 14(8): 491-502.
[30] Palmer JK, van der Pols J C, Sullivan KA, et al.A double-blind randomised controlled trial of prebiotic supplementation in children with autism: Effects on parental quality of life, child behaviour, gastrointestinal symptoms, and the microbiome[J].J Autism Dev Disord, 2025, 55(3): 775-788.
[31] Inoue R, Sakaue Y, Kawada Y, et al.Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder[J].J Clin Biochem Nutr, 2019, 64(3): 217-223.
[32] Tan Q, Orsso CE, Deehan EC, et al.Probiotics, prebiotics, synbiotics, and fecal microbiota transplantation in the treatment of behavioral symptoms of autism spectrum disorder: A systematic review[J].Autism Res, 2021, 14(9): 1820-1836.
[33] Swanson KS, Gibson GR, Hutkins R, et al.The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics[J].Nat Rev Gastroenterol Hepatol, 2020, 17(11): 687-701.
[34] Wang Y, Li N, Yang JJ, et al.Probiotics and fructo-oligosaccharide intervention modulate the microbiota-gut brain axis to improve autism spectrum reducing also the hyper-serotonergic state and the dopamine metabolism disorder[J].Pharmacol Res, 2020, 157: 104784.
[35] Phan J, Calvo DC, Nair D, et al.Precision synbiotics increase gut microbiome diversity and improve gastrointestinal symptoms in a pilot open-label study for autism spectrum disorder[J].mSystems, 2024, 9(5): e0050324.
[36] Wang C, Chen W, Jiang Y, et al.A synbiotic formulation of Lactobacillus reuteri and inulin alleviates ASD-like behaviors in a mouse model: The mediating role of the gut-brain axis[J].Food Funct, 2024, 15(1): 387-400.
[37] Wan L, Wang H, Liang Y, et al.Effect of oral faecal microbiota transplantation intervention for children with autism spectrum disorder: A randomised, double-blind, placebo-controlled trial[J].Clin Transl Med, 2024, 14(9): e70006.
[38] Li N, Chen H, Cheng Y, et al.Fecal microbiota transplantation relieves gastrointestinal and autism symptoms by improving the gut microbiota in an open-label study[J].Front Cell Infect Microbiol, 2021, 11: 759435.
[39] Zhang Y, Zhang J, Pan Z, et al.Effects of washed fecal bacteria transplantation in sleep quality, stool features and autism symptomatology: A Chinese preliminary observational study[J].Neuropsychiatr Dis Treat, 2022, 18: 1165-1173.
[40] Pan ZY, Zhong HJ, Huang DN, et al.Beneficial effects of repeated washed microbiota transplantation in children with autism[J].Front Pediatr, 2022, 10: 928785.