肠道菌群与孤独症谱系障碍的研究进展
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摘要
孤独症谱系障碍(ASD)是一种主要症状为社会交往障碍、重复刻板行为及狭隘兴趣为特征的神经发育障碍性疾病。病因极为复杂,目前集中在遗传及环境因素两大方面。由于发病机制不明,尚无有效的治疗方法。随着对ASD研究的深入,发现ASD患儿普遍存在胃肠道疾病及肠道菌群的改变。最近的研究显示,肠道神经系统和中枢神经系统之间存在双向互动,称之为微生物-肠-脑轴。肠道菌群通过神经内分泌、神经免疫和肠道神经系统调控大脑功能,进而影响大脑发育和行为。故肠道菌群的失衡可能与ASD的发生有关。本文将总结至今肠道菌群对ASD的作用和相关治疗进展。
Autism spectrum disorder(ASD) is a neurodevelopmental disorder mainly characterized by social communication disorders, repetitive behaviors and narrow interests.The etiology of ASD is complex, and it focuses on the genetic and environmental factors.As the pathogenesis is unknown, there is no effective treatment.It is found that gastrointestinal diseases and changes of intestinal flora are common in ASD children.Recent studies have shown a two-way interaction between the gut nervous system and the central nervous system, called the microbiota-gut-brain axis.Gut flora regulates brain function through neuroendocrine, immune and intestinal nervous systems and thus affects brain development and behavior.Therefore, the imbalance of intestinal flora may be related to the occurrence of ASD.This article will summarize the effect of intestinal flora on ASD and the progress of related treatment.
Autism spectrum disorder(ASD) is a neurodevelopmental disorder mainly characterized by social communication disorders, repetitive behaviors and narrow interests.The etiology of ASD is complex, and it focuses on the genetic and environmental factors.As the pathogenesis is unknown, there is no effective treatment.It is found that gastrointestinal diseases and changes of intestinal flora are common in ASD children.Recent studies have shown a two-way interaction between the gut nervous system and the central nervous system, called the microbiota-gut-brain axis.Gut flora regulates brain function through neuroendocrine, immune and intestinal nervous systems and thus affects brain development and behavior.Therefore, the imbalance of intestinal flora may be related to the occurrence of ASD.This article will summarize the effect of intestinal flora on ASD and the progress of related treatment.
引文
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[20] Kang DW, Adams JB, Gregory AC, et al.Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms:an open-label study[J].Microbiome, 2017,5(1):10-13.
[2] Rook GA, Lowry CA, Raison CL, et al.Hygiene and other early childhood influences on the subsequent function of the immune system[J].Brain Research,2014,16(17):47-62.
[3] Chu DM, Antony KM, Ma J, et al.The early infant gut microbiome varies in association with a maternal high-fat diet[J].Genome Med,2016,8(1):77.
[4] Neufeld KAM, Mao YK, Bienenstock J, et al.The microbiome is essential for normal gut intrinsic primary afferent neuron excitability in the mouse[J].Neurogastroenterol Motil,2013,25(2):183-188.
[5] Bravo JA, Forsythe P, Chew MV, et al.Ingestion lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve[J].Proc Natl Acad Sci U S A,2011,108(38) :16050-16055.
[6] Bienenstock J, Kunze W,Forsythe P,et al.The microbiome-gut-brain axis and the consequences of infection and dysbiosis[J].Gastroenterology,2016,3:32-39.
[7] Sudo N, Chida Y, Aiba Y, et al.Postnatal microbial colonization programs the hypothalamic-pituitary-adrenal system for stress response in mice[J].Physiol,2004,558(1):263-275.
[8] Yarandi SS, Peterson DA, Treisman GJ, et al.Modulatory effects of gut microbiota on the central nervous system:how gut could play a role in neuropsychiatric health and diseases[J].Neurogastroenterol Motil,2016,22:201-212.
[9] Sharon G, Sampson TR,Geschwind DH, et al.The central nervous system and the gut microbiome[J].Cell, 2016,167:915-932.
[10] Ricci S,Businaro R, Ippoliti F, et al.Altered cytokine and BDNF levels in autism spectrum disorder[J].Neurotox Res,2013,24(4):491-501.
[11] Madore C, Leyrolle Q, Lacabanne C, et al.Neuroinflammation in Autism:plausible role of maternal in ammation, dietary omega 3 and microbiota[J].Neural Plast,2016:1-15.doi:10.1155/2016/3597209.
[12] Erny D, de Agelis ALH, Jaitin D, et al.Host microbiota constantly control maturation and functiom of mocroglia in the CNS[J].Nat Neurosci,2015,18(7):965-977.
[13] Belger A, Carpenter KL, Yucel GH, et al.The neural circuitry of autism[J].Neurotox Res,2011,20:201-214.
[14] Russo FB,Freitas BC, Pignatari GC, et al.Modeling the interplay between neurons and astrocytes in autism using human induced pluripotent stem cells[j].Biol Psychiatry,2017,18(9):154-156.
[15] De Angelis M, Piccolo M,Vannini L, et al.Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified[J].PLoS One,2013,8(10):e76993.
[16] Nankova BB, Agarwal R, MacFabe DF, et al.Enteric bacterial metabolites propionic and butyric acid modulate gene expression, including CREB-dependent catecholaminergic neurotransmission in PC12 cells-possible relevance to autism spectrum disorders[J].PLoS One 2014,9:e103740.
[17] Kim N, Yun M, Oh YJ, et al.Mind-altering with the gut:Modulation of the gut-brain axis with probiotics[J].Microbiol,2018,56(3):172-182.
[18] Janik R, Thomason LAM, Stanisz AM,et al.Magnetic resonance spectroscopy reveals oral Lactobacillus promotion of increases in brain GABA,cetyl aspartate and glutamate[J].Neuroimage,2016,125:988-995.
[19] Liu X, Cao S, Zhang X, et al.Modulation of gut microbiota- brain axis by probiotics, prebiotics and diet[J].Agric Food Chem, 2015,63:7885-7895.
[20] Kang DW, Adams JB, Gregory AC, et al.Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms:an open-label study[J].Microbiome, 2017,5(1):10-13.