肠道微生物与儿童孤独症谱系障碍的研究进展

doi:10.11852/zgetbjzz2019-0134

摘要/Abstract

摘要： 孤独症谱系障碍(ASD)是一种严重的神经系统广泛性发育障碍疾病,其核心症状是社会功能的缺失,社会交流障碍、兴趣范围局限及刻板行为等,由遗传和环境因素相互作用而引起。肠道微生物是存在于肠道中数量众多的微生物,不仅影响消化吸收能力,而且通过肠-脑轴影响大脑的发育和功能。特定的益生菌可以调节人体微生态的平衡,维持正常的代谢吸收和免疫防御功能。婴幼儿发育关键期肠道微生物失调会增加儿童ASD的风险,并通过神经内分泌、免疫、代谢产物途径影响儿童ASD的发展,益生菌治疗有望成为治疗儿童ASD的新型辅助治疗方法

关键词: 肠道微生物, 孤独症谱系障碍, 儿童

Abstract: Autism spectrum disorders(ASD)is a serious neurodevelopmental disorder,and its core symptoms include the lack of social function,social communication barriers,limitations of interest and stereotyped behavior,caused by the interaction of genetic and environmental factors. Intestinal microorganisms are a large number of microorganisms present in the intestine,which not only affect the ability to digest and absorb,but also affect the brain development and function through the gut-brain axis. Specific probiotics can regulate the balance of human micro-ecology,maintain normal metabolic absorption and immune defense functions. Intestinal microbial disorders in critical stages of infant development may increase the risk of ASD,and affect the development of ASD in children through neuroendocrine,immune,and metabolite pathways. Therefore,probiotics treatment is promising to be a new adjuvant treatment for ASD.

Key words: intestinal microorganisms, autism spectrum disorder, children

中图分类号:

R749.94

白茂飞, 王霞. 肠道微生物与儿童孤独症谱系障碍的研究进展[J]. 中国儿童保健杂志, 2019, 27(9): 986-989.

BAI Mao-fei, WANG Xia. Research advances on intestinal microbes and childhood autism spectrum disorders[J]. journal1, 2019, 27(9): 986-989.

参考文献

[1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders[M]. 5th ed. Arlington:American Psychiatric Publishing,2013.
[2] Kim YS,Leventhal BL. Genetic epidemiology and insights into interactive genetic and environmental effects in autism spectrum disorders[J]. Biol Psychiatry,2015,77(1):66-74.
[3] Colvert E,Tick B,Mcewen F,et al. Heritability of autism spectrum disorder in a UK population-based twin sample[J]. JAMA Psychiatry,2015,72(5):415-423.
[4] Fung TC,Olson CA,Hsiao EY. Interactions between the microbiota,immune and nervoussystems in health and disease[J]. Nat Neurosci,2017,20(2):145-155.
[5] Peters B,Williams KC,Gorrindo P,et al. Rigid-compulsive behaviors are associated with mixed bowel symptoms in autism spectrum disorder[J]. J Autism Dev Disord,2014,44(6):1425-1432.
[6] Maenner MJ,Arneson CL,Levy SE,et al. Brief report:association between behavioral features and gastrointestinal problems among children with autism spectrum disorder[J]. J Autism Dev Disord,2012,42(7):1520-1525.
[7] Finegold SM,Dowd SE,Gontcharova V,et al. Pyrosequencing study of fecal microflora of autistic and control children[J]. Anaerobe,2010,16(4):444-453.
[8] Mayer EA,Padua D,Tillisch K. Altered brain-gut axis in autism:comorbidity or causative mechanisms?[J]. Bioessays,2014,36(10):933-939.
[9] Ashwood P,Krakowiak P,Hertz-Picciotto I,et al. Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome[J]. Brain Behav Immun,2011,25(1):40-45.
[10] Carabotti M,Scirocco A,Maselli MA,et al. The gut-brain axis:interactions between enteric microbiota,central and enteric nervous systems[J]. Ann Gastroenterol,2015,28(2):203-209.
[11] Yano JM,Yu K,Donaldson GP,et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis[J]. Cell,2015,161(2):264-276.
[12] O′Mahony SM,Clarke G,Borre YE,et al. Serotonin,tryptophan metabolism and the brain-gut-microbiome axis[J]. Behav Brain Res,2015,277:32-48.
[13] 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.
[14] Patterson E,Cryan JF,Fitzgerald GF,et al. Gut microbiota,the pharmabiotics they produce and host health[J]. Proc Nutr Soc,2014,73(4):477-489.
[15] Wang L,Christophersen CT,Sorich MJ,et al. Elevated fecal short chain fatty acid and ammonia concentrations in children with autism spectrum disorder[J]. Dig Dis Sci,2012,57(8):2096-2102.
[16] Shultz SR,MacFabe DF,Ossenkopp KP,et al. Intracerebroventricular injection of propionic acid,an enteric bacterial metabolic end-product,impairs social behavior in the rat:implications for an animal model of autism[J]. Neuropharmacology,2008,54(6):901-911.
[17] Coury DL,Ashwood P,Fasano A,et al. Gastrointestinal conditions in children with autism spectrum disorder:developing a research agenda[J]. Pediatrics,2012,130(Suppl 2):160-168.
[18] De Vadder F,Kovatcheva-Datchary P,Goncalves D,et al. Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits[J]. Cell,2014,156(1-2):84-96.
[19] 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.
[20] Finegold SM,Summanen PH,Downes J,et al. Detection of clostridium perfringens toxin genes in the gut microbiota of autistic children[J]. Anaerobe,2017,45:133-137.
[21] Coretti L,Cristiano C,Florio E,et al. Sex-related alterations of gut microbiota composition in the BTBR mouse model of autism spectrum disorder[J]. Sci Rep,2017,7(1):45356.
[22] Tomova A,Husarova V,Lakatosova S,et al. Gastrointestinal microbiota in children with autism in Slovakia[J]. Physiol Behav,2015,138:179-187.
[23] Hsiao EY,Mcbride SW,Hsien S,et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders[J]. Cell,2013,155(7):1451-1463.
[24] Iovene MR,Bombace F,Maresca R,et al. Intestinal dysbiosis and yeast isolation in stool of subjects with autism spectrum disorders[J]. Mycopathologia,2017,182(3-4):349-363.
[25] Burrus CJ. A biochemical rationale for the interaction between gastrointestinal yeast and autism[J]. Med Hypotheses,2012,79(6):784-785.
[26] Zelante T,Iannitti RG,Cunha C,et al. Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22[J]. Immunity,2013,39(2):372-385.
[27] Adams JB,Johansen LJ,Powell LD,et al. Gastrointestinal flora and gastrointestinal statusin children with autism--comparisons to typical children and correlation with autism severity[J]. BMC Gastroenterol,2011,11:22.
[28] Atladóttir HO,Thorsen P,østergaard L,et al. Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders[J]. J Autism Dev Disord,2010,40(12):1423-1430.
[29] Brimberg L,Sadiq A,Gregersen PK,et al. Brain-reactive IgG correlates with autoimmunity in mothers of a child with an autism spectrum disorder[J]. Mol Psychiatry,2013,18(11):1171-1177.
[30] 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.
[31] Gondalia SV,Palombo EA,Knowles SR,et al. Molecular characterisation of gastrointestinal microbiota of children with autism(with and without gastrointestinal dysfunction) and their neurotypical siblings[J]. Autism Res,2012,5(6):419-427.
[32] Chaidez V,Hansen RL,Hertz-Picciotto I. Gastrointestinal problems in children with autism,developmental delays or typical development[J]. J Autism Dev Disord,2014,44(5):1117-1127.
[33] Satokari R,Grönroos T,Laitinen K,et al. Bifidobacterium and lactobacillus DNA in the human placenta[J]. Lett Appl Microbiol,2009,48(1):8-12.
[34] Bokulich NA,Chung J,Battaglia T,et al. Antibiotics,birth mode,and diet shape microbiome maturation during early life[J]. Sci Transl Med,2016,8(343):343-382.
[35] Borre YE,O′Keeffe GW,Clarke G,et al. Microbiota and neurodevelopmental windows:implications for brain disorders[J]. Trends Mol Med,2014,20(9):509-518.
[36] Dinan TG,Cryan JF. Gut instincts:microbiota as a key regulator of brain development,ageing and neurodegeneration[J]. J Physiol,2017,595(2):489-503.
[37] Buffington SA,Di Prisco GV,Auchtung TA,et al. Microbial reconstitution reverses maternal diet-induced social and synaptic deficits in offspring[J]. Cell,2016,165(7):1762-1775.
[38] Kumar H,Sharma B. Minocycline ameliorates prenatalvalproic acid induced autistic behaviour,biochemistry and blood brain barrier impairments in rats[J]. Brain Res,2016,1630:83-97.
[39] Urbano M,Okwara L,Manser P,et al. A trial of d-cycloserine to treat stereotypies in older adolescents and young adults with autism spectrum disorder[J]. Clin Neuropharmacol,2014,37(3):69-72.
[40] Shaaban SY,Gendy YG,Mehanna NS,et al. The role of probiotics in children with autism spectrum disorder:a prospective,open-label study[J]. Nutr Neurosci,2018,21(9):676-681.