肠道微生物及其代谢产物与孤独症谱系障碍的研究进展

刘欢; 王锁英; 李玉勤; 孙志明

doi:10.11852/zgetbjzz2021-0627

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中国儿童保健杂志 ›› 2022, Vol. 30 ›› Issue (11) : 1216-1220. DOI: 10.11852/zgetbjzz2021-0627

综述

肠道微生物及其代谢产物与孤独症谱系障碍的研究进展

刘欢¹, 王锁英¹, 李玉勤¹, 孙志明²

作者信息 +

Research progress on intestinal microbes and their metabolites and autism spectrum disorder

LIU Huan^*, WANG Suo-ying, LI Yu-qin, SUN Zhi-ming

Author information +

文章历史 +

摘要

目前,孤独症谱系障碍(ASD)病因和表现的潜在机制仍然知之甚少。越来越多的研究表明,肠道微生物及其代谢产物(如短链脂肪酸、γ-氨基丁酸等)的改变可能与ASD的发病有关。因此,本文将ASD儿童肠道微生物和代谢物的变化及机制的相关研究进行综述,分析ASD儿童和健康儿童之间可能存在的肠道微生物与代谢产物的差异及联系,以探讨肠道微生物及其代谢物的变化对ASD患儿的影响,为ASD的诊断和治疗提供一些新的思路。

Abstract

Currently, the underlying mechanisms of etiology and manifestations ofautism spectrum disorder (ASD) are still poorly understood.More and more studies have shown that changes in intestinal microbes and their metabolites (such as short-chain fatty acids, γ-aminobutyric acid, etc.) may be related to the pathogenesis of ASD.Therefore, this paper reviews the studies related to the changes and mechanisms of gut microbes and metabolites in ASD children, and analyzes the possible differences and associations of gut microbes and metabolites between ASD children and healthy children, in order to explore the influence of changes in intestinal microbes and their metabolites on children ASD, and to provide some new ideas for the diagnosis and treatment of ASD.

导出引用

刘欢, 王锁英, 李玉勤, 孙志明. 肠道微生物及其代谢产物与孤独症谱系障碍的研究进展[J]. 中国儿童保健杂志. 2022, 30(11): 1216-1220 https://doi.org/10.11852/zgetbjzz2021-0627

LIU Huan, WANG Suo-ying, LI Yu-qin, SUN Zhi-ming. Research progress on intestinal microbes and their metabolites and autism spectrum disorder[J]. Chinese Journal of Child Health Care. 2022, 30(11): 1216-1220 https://doi.org/10.11852/zgetbjzz2021-0627

中图分类号： R749.94

参考文献

[1] American Psychiatric Association.Diagnostic and statistical manual of mental disorder (DSM-5)[M].Washington DC: Pilgrim Press,2013.
[2] Landa R, Garrett-Mayer E.Development in infants with autism spectrum disorders: A prospective study[J].J Child Psychol Psychiatry, 2006, 47(6):629-638.
[3] Maenner MJ, Shaw KA, Bakian AV, et al.Prevalence of autism spectrum disorder among children aged 8 years-autism and developmental disabilities monitoring network, 11 sites, United States, 2018[J].MMWR Surveill Summ, 2021, 70(11):1-16.
[4] Zhou H, Xu X, Yan W, et al.Prevalence of autism spectrum disorder in China: A nationwide multi-center population-based study among children aged 6 to 12 years[J].Neurosci Bull, 2020, 36(9):961-971.
[5] Thulasi V, Steer RA, Monteiro IM, et al.Overall severities of gastrointestinal symptoms in pediatric outpatients with and without autism spectrum disorder[J].Autism, 2019, 23(2):524-530.
[6] Yang XL, Liang S, Zou MY, et al.Are gastrointestinal and sleep problems associated with behavioral symptoms of autism spectrum disorder? [J].Psychiatry Res, 2018, 259:229-235.
[7] Wang L, Yu YM, Zhang YQ, et al.Hydrogen breath test to detect small intestinal bacterial overgrowth: A prevalence case-control study in autism[J].Eur Child Adolesc Psychiatry, 2018, 27(2):233-240.
[8] Stewart CJ,Ajami NJ, O'Brien JL, et al.Temporal development of the gut microbiome in early childhood from the TEDDY study[J].Nature, 2018, 562(7728):583-588.
[9] Fung TC, Olson CA, Hsiao EY.Interactions between the microbiota, immune and nervous systems in health anddisease[J].Nat Neurosci, 2017, 20(2):145-155.
[10] Finegold SM, Molitoris D, Song Y, et al.Gastrointestinal microflora studies in late-onset autism[J].Clin Infect Dis, 2002, 35(Suppl 1):6-16.
[11] Stiles BG, Pradhan K, Fleming JM,et al.Clostridium and bacillus binary enterotoxins:Bad for the bowels, and eukaryotic being[J].Toxins (Basel), 2014, 6(9):2626-2656.
[12] Liu S, Li E, Sun Z, et al.Altered gut microbiota and short chain fatty acids in Chinese children with autism spectrumdisorder[J].Sci Rep, 2019, 9(1):287.
[13] 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.
[14] Wang M, Wan J,Rong H, et al.Alterations in gut glutamate metabolism associated with changes in gut microbiota composition in children with autism spectrum disorder[J].mSystems, 2019, 4(1):e00321-18.
[15] Tomova A, Husarova V, Lakatosova S, et al.Gastrointestinal microbiota in children with autism in Slovakia[J].Physiol Behav, 2015, 138:179-187.
[16] Kang DW, Adams JB,Vargason T, et al.Distinct fecal and plasma metabolites in children with autism spectrum disorders and their modulation after microbiota transfer therapy[J].mSphere, 2020, 5(5):e00314-20.
[17] Sharon G, Cruz NJ, Kang DW, et al.Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice[J].Cell, 2019, 177(6):1600-1618.
[18] Wang Y, Li N, Yang JJ, et al.Probiotics andfructo-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.
[19] Guo M, Zhu J, Yang T, et al.Vitamin A improves the symptoms of autism spectrum disorders and decreases 5-hydroxytryptamine (5-HT): A pilot study[J].Brain Res Bull, 2018, 137:35-40.
[20] Pascucci T, Colamartino M, Fiori E, et al.P-cresol alters brain dopamine metabolism and exacerbates autism-like behaviors in the btbr mouse[J].Brain Sci, 2020, 10(4):233.
[21] Buffington SA, DiPrisco GV, Auchtung TA, et al.Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring[J].Cell, 2016, 165(7):1762-1775.
[22] Peng L, Li ZR, Green RS,et al.Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers[J].J Nutr, 2009, 139(9):1619-1625.
[23] Huang H, Liu JQ, Yu Y, et al.Regulation of TWIK-related potassium channel-1 (Trek1) restitutes intestinal epithelial barrierfunction[J].Cell Mol Immunol, 2016, 13(1):110-118.
[24] Sherry CL, Kim SS,Dilger RN, et al.Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization[J].Brain Behav Immun, 2010, 24(4):631-640.
[25] Abdelli LS, Samsam A, Naser SA.Propionic acid induces gliosis and neuro-inflammation through modulation of PTEN/AKT pathway in autism spectrum disorder[J].Sci Rep, 2019, 9(1):8824.
[26] Shams S, Foley KA,Kavaliers M, et al.Systemic treatment with the enteric bacterial metabolic product propionic acid results in reduction of social behavior in juvenile rats: Contribution to a rodent model of autism spectrum disorder[J].Dev Psychobiol, 2019, 61(5):688-699.
[27] Meeking MM, MacFabe DF, Mepham JR, et al.Propionic acid induced behavioural effects of relevance to autism spectrum disorder evaluated in the hole board test with rats[J].Prog Neuropsychopharmacol Biol Psychiatry, 2020, 97:109794.
[28] Puts NAJ,Wodka EL, Harris AD, et al.Reduced GABA and altered somatosensory function in children with autism spectrum disorder[J].Autism Res, 2017, 10(4):608-619.
[29] Kirkovski M, Suo C, Enticott PG, et al.Short communication: Sex-linked differences in gamma-aminobutyric acid (GABA) are related to social functioning in autism spectrum disorder[J].Psychiatry Res Neuroimaging, 2018, 274:19-22.
[30] Horder J, Petrinovic MM, Mendez MA, et al.Glutamate and GABA in autism spectrum disorder-a translational magnetic resonance spectroscopy study in man and rodent models[J].Transl Psychiatry, 2018, 8(1):106.
[31] Carvalho Pereira A, Violante IR, Mouga S, et al.Medial frontal lobe neurochemistry in autism spectrum disorder is marked by reduced N-acetylaspartate and unchanged gamma-aminobutyric acid and glutamate+glutamine levels[J].J Autism Dev Disord, 2018, 48(5):1467-1482.
[32] Han S, Tai C, Jones CJ, et al.Enhancement of inhibitory neurotransmission by GABAA receptors having α2,3-subunits ameliorates behavioral deficits in a mouse model of autism[J].Neuron, 2014, 81(6):1282-1289.
[33] Yano JM, Yu K, Donaldson GP, et al.Indigenous bacteria from the gut microbiota regulate host serotoninbiosynthesis[J].Cell, 2015, 161(2):264-276.
[34] Walsh JJ,Christoffel DJ, Heifets BD, et al.5-HT release in nucleus accumbens rescues social deficits in mouse autism model[J].Nature, 2018, 560(7720):589-594.
[35] Golubeva AV, Joyce SA, Moloney G, et al.Microbiota-related changes in bile Acid & tryptophan metabolism are associated with gastrointestinal dysfunction in a mouse model of autism[J]. EBioMedicine, 2017, 24:166-178.
[36] Lai MC, Lombardo MV, Baron-Cohen S.Autism[J].Lancet, 2014, 383(9920):896-910.
[37] Sharma SR,Gonda X, Tarazi FI.Autism spectrum disorder: classification, diagnosis and therapy[J].Pharmacol Ther, 2018, 190:91-104.
[38] Kang DW, Adams JB, Gregory AC, et al.Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-labelstudy[J].Microbiome, 2017, 5(1):10.