脑-肠轴视角下母源因素影响子代孤独症谱系障碍患病风险的研究进展

丁浩波; 李闯; 武书丽

doi:10.7499/j.issn.1008-8830.2511143

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中国当代儿科杂志 ›› 2026, Vol. 28 ›› Issue (4) : 514-521. DOI: 10.7499/j.issn.1008-8830.2511143

综述

脑-肠轴视角下母源因素影响子代孤独症谱系障碍患病风险的研究进展

丁浩波 ¹^,² ,
李闯 ¹^,² (综述) ,
武书丽 ¹^,² (审校)

作者信息 +

Research progress on maternal factors influencing the risk of autism spectrum disorder in offspring from a gut-brain axis perspective

Hao-Bo DING ¹^,² ,
Chuang LI ¹^,² ,
Shu-Li WU ¹^,²

Author information +

文章历史 +

摘要

孤独症谱系障碍（autism spectrum disorder, ASD）是一类以社会交往障碍和重复刻板行为为核心特征的神经发育性障碍。母体孕期环境因素被认为是子代ASD发生的重要危险因素，其机制涉及母体与子代肠道菌群紊乱、免疫失调、代谢异常及神经炎症等。特定益生菌干预通过调节肠道菌群结构、改善肠道屏障功能以及调控炎症反应和神经信号通路，在孕期及生命早期展现出预防与改善ASD的潜力。该文从脑-肠轴视角系统综述母源因素影响子代ASD风险的相关机制及潜在干预策略，以期为ASD的早期预防与干预提供理论依据和新的研究思路。

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core features of social communication deficits and repetitive, stereotyped behaviors. Maternal environmental factors during pregnancy are considered important risk factors for ASD in offspring, with mechanisms involving dysbiosis of the maternal and offspring gut microbiota, immune dysregulation, metabolic abnormalities, and neuroinflammation. Specific probiotic interventions show potential during pregnancy and early life to prevent and ameliorate ASD by modulating gut microbiota composition, improving intestinal barrier function, and regulating inflammatory responses and neural signaling pathways. This review systematically summarizes, from a gut-brain axis perspective, the mechanisms by which maternal factors influence ASD risk in offspring and the potential intervention strategies, aiming to provide a theoretical basis and new research directions for the early prevention and intervention of ASD.

导出引用

丁浩波, 李闯, 武书丽. 脑-肠轴视角下母源因素影响子代孤独症谱系障碍患病风险的研究进展[J]. 中国当代儿科杂志. 2026, 28(4): 514-521 https://doi.org/10.7499/j.issn.1008-8830.2511143

Hao-Bo DING, Chuang LI, Shu-Li WU. Research progress on maternal factors influencing the risk of autism spectrum disorder in offspring from a gut-brain axis perspective[J]. Chinese Journal of Contemporary Pediatrics. 2026, 28(4): 514-521 https://doi.org/10.7499/j.issn.1008-8830.2511143

参考文献

列表( 原文顺序 | 文献年度倒序 | 文中引用次数倒序 ) 可视化分析

[1]	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. 孤独症谱系障碍儿童早期识别筛查和早期干预专家共识[J]. 中华儿科杂志, 2017, 55(12): 890-897. DOI: 10.3760/cma.j.issn.0578-1310.2017.12.004 . https://www.ncbi.nlm.nih.gov/pubmed/29262466 本文引用 [1]

[2]	Zeidan J, Fombonne E, Scorah J, et al. Global prevalence of autism: a systematic review update[J]. Autism Res, 2022, 15(5): 778-790. PMCID: PMC9310578. DOI: 10.1002/aur.2696 . https://www.ncbi.nlm.nih.gov/pubmed/35238171 本文引用 [1]

[3]

Maenner

, Warren

, Williams

, 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. PMCID: PMC10042614. DOI: 10.15585/mmwr.ss7202a1 .

https://www.ncbi.nlm.nih.gov/pubmed/36952288

本文引用 [1]

[4]	Sun X, Allison C, Wei L, et al. Autism prevalence in China is comparable to Western prevalence[J]. Mol Autism, 2019, 10: 7. PMCID: PMC6394100. DOI: 10.1186/s13229-018-0246-0 . https://www.ncbi.nlm.nih.gov/pubmed/30858963 本文引用 [1]

[5]	Hirota T, King BH. Autism spectrum disorder: a review[J]. JAMA, 2023, 329(2): 157-168. DOI: 10.1001/jama.2022.23661 . https://www.ncbi.nlm.nih.gov/pubmed/36625807 本文引用 [1]

[6]	Husso A, Pessa-Morikawa T, Koistinen VM, et al. Impacts of maternal microbiota and microbial metabolites on fetal intestine, brain, and placenta[J]. BMC Biol, 2023, 21(1): 207. PMCID: PMC10552303. DOI: 10.1186/s12915-023-01709-9 . https://www.ncbi.nlm.nih.gov/pubmed/37794486 本文引用 [1]

[7]

Fehr

, Moossavi

, Sbihi

, et al. Breastmilk feeding practices are associated with the co-occurrence of bacteria in mothers' milk and the infant gut: the CHILD cohort study[J]. Cell Host Microbe, 2020, 28(2): 285-297.e4. DOI: 10.1016/j.chom.2020.06.009 .

https://www.ncbi.nlm.nih.gov/pubmed/32652062

本文引用 [2]

[8]	Ma J, Li Z, Zhang W, et al. Comparison of gut microbiota in exclusively breast-fed and formula-fed babies: a study of 91 term infants[J]. Sci Rep, 2020, 10(1): 15792. PMCID: PMC7519658. DOI: 10.1038/s41598-020-72635-x . https://www.ncbi.nlm.nih.gov/pubmed/32978424 本文引用 [1]

[9]	Mitchell CM, Mazzoni C, Hogstrom L, et al. Delivery mode affects stability of early infant gut microbiota[J]. Cell Rep Med, 2020, 1(9): 100156. PMCID: PMC7762768. DOI: 10.1016/j.xcrm.2020.100156 . https://www.ncbi.nlm.nih.gov/pubmed/33377127 本文引用 [2]

[10]	Shao Y, Forster SC, Tsaliki E, et al. Stunted microbiota and opportunistic pathogen colonization in caesarean-section birth[J]. Nature, 2019, 574(7776): 117-121. PMCID: PMC6894937. DOI: 10.1038/s41586-019-1560-1 . https://www.ncbi.nlm.nih.gov/pubmed/31534227 本文引用 [1]

[11]	Laue HE, Coker MO, Madan JC. The developing microbiome from birth to 3 years: the gut-brain axis and neurodevelopmental outcomes[J]. Front Pediatr, 2022, 10: 815885. PMCID: PMC8936143. DOI: 10.3389/fped.2022.815885 . https://www.ncbi.nlm.nih.gov/pubmed/35321011 本文引用 [1]

[12]	Lynch CMK, Cowan CSM, Bastiaanssen TFS, et al. Critical windows of early-life microbiota disruption on behaviour, neuroimmune function, and neurodevelopment[J]. Brain Behav Immun, 2023, 108: 309-327. DOI: 10.1016/j.bbi.2022.12.008 . https://www.ncbi.nlm.nih.gov/pubmed/36535610 本文引用 [1]

[13]

Zuffa

, Schimmel

, Gonzalez-Santana

, et al. Early-life differences in the gut microbiota composition and functionality of infants at elevated likelihood of developing autism spectrum disorder[J]. Transl Psychiatry, 2023, 13(1): 257. PMCID: PMC10344877. DOI: 10.1038/s41398-023-02556-6 .

https://www.ncbi.nlm.nih.gov/pubmed/37443359

本文引用 [2]

[14]	Ahrens AP, Hyötyläinen T, Petrone JR, et al. Infant microbes and metabolites point to childhood neurodevelopmental disorders[J]. Cell, 2024, 187(8): 1853-1873.e15. DOI: 10.1016/j.cell.2024.02.035 . https://www.ncbi.nlm.nih.gov/pubmed/38574728 本文引用 [1]

[15]	Laue HE, Bonham KS, Coker MO, et al. Prospective association of the infant gut microbiome with social behaviors in the ECHO consortium[J]. Mol Autism, 2024, 15(1): 21. PMCID: PMC11101342. DOI: 10.1186/s13229-024-00597-2 . https://www.ncbi.nlm.nih.gov/pubmed/38760865 本文引用 [1]

[16]	Koren O, Konnikova L, Brodin P, et al. The maternal gut microbiome in pregnancy: implications for the developing immune system[J]. Nat Rev Gastroenterol Hepatol, 2024, 21(1): 35-45. PMCID: PMC12635954. DOI: 10.1038/s41575-023-00864-2 . https://www.ncbi.nlm.nih.gov/pubmed/38097774 本文引用 [3]

[17]	Saigh BH. Breastfeeding duration and neurodevelopment: insights into autism spectrum disorders and weaning practices[J]. J Health Popul Nutr, 2025, 44(1): 62. PMCID: PMC11877936. DOI: 10.1186/s41043-025-00784-8 . https://www.ncbi.nlm.nih.gov/pubmed/40033428 本文引用 [2]

[18]	Deng W, Yi P, Xiong Y, et al. Gut metabolites acting on the gut-brain axis: regulating the functional state of microglia[J]. Aging Dis, 2024, 15(2): 480-502. PMCID: PMC10917527. DOI: 10.14336/AD.2023.0727 . https://www.ncbi.nlm.nih.gov/pubmed/37548933 本文引用 [1]

[19]

Caputi

, Hill

, Figueiredo

, et al. Functional contribution of the intestinal microbiome in autism spectrum disorder, attention deficit hyperactivity disorder, and Rett syndrome: a systematic review of pediatric and adult studies[J]. Front Neurosci, 2024, 18: 1341656. PMCID: PMC10954784. DOI: 10.3389/fnins.2024.1341656 .

https://www.ncbi.nlm.nih.gov/pubmed/38516317

本文引用 [2]

[20]	Fahur Bottino G, Bonham KS, Patel F, et al. Early life microbial succession in the gut follows common patterns in humans across the globe[J]. Nat Commun, 2025, 16(1): 660. PMCID: PMC11733223. DOI: 10.1038/s41467-025-56072-w . https://www.ncbi.nlm.nih.gov/pubmed/39809768 本文引用 [1]

[21]	Di Gesù CM, Buffington SA. The early life exposome and autism risk: a role for the maternal microbiome?[J]. Gut Microbes, 2024, 16(1): 2385117. PMCID: PMC11318715. DOI: 10.1080/19490976.2024.2385117 . https://www.ncbi.nlm.nih.gov/pubmed/39120056 本文引用 [1]

[22]

Agrawal

, Rath

, Rao

, et al. Critical appraisal of systematic reviews assessing gut microbiota and effect of probiotic supplementation in children with ASD: an umbrella review[J]. Microorganisms, 2025, 13(3): 545. PMCID: PMC11946400. DOI: 10.3390/microorganisms13030545 .

https://www.ncbi.nlm.nih.gov/pubmed/40142438

本文引用 [1]

[23]

Holingue

, Brucato

, Ladd-Acosta

, et al. Interaction between maternal immune activation and antibiotic use during pregnancy and child risk of autism spectrum disorder[J]. Autism Res, 2020, 13(12): 2230-2241. PMCID: PMC7839062. DOI: 10.1002/aur.2411 .

https://www.ncbi.nlm.nih.gov/pubmed/33067915

本文引用 [2]

[24]	Zappala C, Barrios CD, Depino AM. Social deficits in mice prenatally exposed to valproic acid are intergenerationally inherited and rescued by social enrichment[J]. Neurotoxicology, 2023, 97: 89-100. DOI: 10.1016/j.neuro.2023.05.009 . https://www.ncbi.nlm.nih.gov/pubmed/37207798 本文引用 [4]

[25]	Kwon HK, Choi GB, Huh JR. Maternal inflammation and its ramifications on fetal neurodevelopment[J]. Trends Immunol, 2022, 43(3): 230-244. PMCID: PMC9005201. DOI: 10.1016/j.it.2022.01.007 . https://www.ncbi.nlm.nih.gov/pubmed/35131181 本文引用 [1]

[26]	Harshaw C, Kojima S, Wellman CL, et al. Maternal antibiotics disrupt microbiome, behavior, and temperature regulation in unexposed infant mice[J]. Dev Psychobiol, 2022, 64(6): e22289. PMCID: PMC9236156. DOI: 10.1002/dev.22289 . https://www.ncbi.nlm.nih.gov/pubmed/35748626 本文引用 [1]

[27]	Love C, Sominsky L, O'Hely M, et al. Prenatal environmental risk factors for autism spectrum disorder and their potential mechanisms[J]. BMC Med, 2024, 22(1): 393. PMCID: PMC11404034. DOI: 10.1186/s12916-024-03617-3 . https://www.ncbi.nlm.nih.gov/pubmed/39278907 本文引用 [1]

[28]	Miyoshi J, Hisamatsu T. The impact of maternal exposure to antibiotics on the development of child gut microbiome[J]. Immunol Med, 2022, 45(2): 63-68. DOI: 10.1080/25785826.2021.1963189 . https://www.ncbi.nlm.nih.gov/pubmed/34392799 本文引用 [1]

[29]	White ND. Drug-induced microbiome changes: considerations in pregnancy[J]. Am J Lifestyle Med, 2023, 17(1): 50-53. PMCID: PMC9830251. DOI: 10.1177/15598276221130259 . https://www.ncbi.nlm.nih.gov/pubmed/36636397 本文引用 [1]

[30]	Gholamalizadeh H, Amiri-Shahri M, Rasouli F, et al. DNA methylation in autism spectrum disorders: biomarker or pharmacological target?[J]. Brain Sci, 2024, 14(8): 737. PMCID: PMC11352561. DOI: 10.3390/brainsci14080737 . https://www.ncbi.nlm.nih.gov/pubmed/39199432 本文引用 [1]

[31]	Xu Y, Yang X, Chen D, et al. Maternal exposure to pesticides and autism or attention-deficit/hyperactivity disorders in offspring: a meta-analysis[J]. Chemosphere, 2023, 313: 137459. PMCID: PMC9839607. DOI: 10.1016/j.chemosphere.2022.137459 . https://www.ncbi.nlm.nih.gov/pubmed/36470360 本文引用 [2]

[32]	Afroz KF, Alviña K. Maternal elevated salt consumption and the development of autism spectrum disorder in the offspring[J]. J Neuroinflammation, 2019, 16(1): 265. PMCID: PMC6911292. DOI: 10.1186/s12974-019-1666-2 . https://www.ncbi.nlm.nih.gov/pubmed/31837704 本文引用 [1]

[33]	Alamoudi RA, Al-Jabri BA, Alsulami MA, et al. Prenatal maternal stress and the severity of autism spectrum disorder: a cross-sectional study[J]. Dev Psychobiol, 2023, 65(2): e22369. DOI: 10.1002/dev.22369 . https://www.ncbi.nlm.nih.gov/pubmed/36811367 本文引用 [2]

[34]	Urbonaite G, Knyzeliene A, Bunn FS, et al. The impact of maternal high-fat diet on offspring neurodevelopment[J]. Front Neurosci, 2022, 16: 909762. PMCID: PMC9354026. DOI: 10.3389/fnins.2022.909762 . https://www.ncbi.nlm.nih.gov/pubmed/35937892 本文引用 [1]

[35]	Kim H. Visualization of maternal IL-17a across the placental membrane[J]. Sci Prog, 2023, 106(3): 368504231195500. PMCID: PMC10467380. DOI: 10.1177/00368504231195500 . https://www.ncbi.nlm.nih.gov/pubmed/37643019 本文引用 [1]

[36]	Sasaki T, Tome S, Takei Y. Intraventricular IL-17A administration activates microglia and alters their localization in the mouse embryo cerebral cortex[J]. Mol Brain, 2020, 13(1): 93. PMCID: PMC7298827. DOI: 10.1186/s13041-020-00635-z . https://www.ncbi.nlm.nih.gov/pubmed/32546246 本文引用 [1]

[37]

Gomes

AKS

, Dantas

, Yokota

, et al. Interleukin-17a induces neuronal differentiation of induced-pluripotent stem cell-derived neural progenitors from autistic and control subjects[J]. Front Neurosci, 2022, 16: 828646. PMCID: PMC8964130. DOI: 10.3389/fnins.2022.828646 .

https://www.ncbi.nlm.nih.gov/pubmed/35360153

本文引用 [1]

[38]	Vuong HE, Pronovost GN, Williams DW, et al. The maternal microbiome modulates fetal neurodevelopment in mice[J]. Nature, 2020, 586(7828): 281-286. PMCID: PMC7554197. DOI: 10.1038/s41586-020-2745-3 . https://www.ncbi.nlm.nih.gov/pubmed/32968276 本文引用 [1]

[39]	Zhang M, Shi Z, Wu C, et al. Cushing syndrome is associated with gut microbial dysbiosis and cortisol-degrading bacteria[J]. J Clin Endocrinol Metab, 2024, 109(6): 1474-1484. DOI: 10.1210/clinem/dgad766 . https://www.ncbi.nlm.nih.gov/pubmed/38157274 本文引用 [1]

[40]

Wampach

, Heintz-Buschart

, Hogan

, et al. Colonization and succession within the human gut microbiome by archaea, bacteria, and microeukaryotes during the first year of life[J]. Front Microbiol, 2017, 8: 738. PMCID: PMC5411419. DOI: 10.3389/fmicb.2017.00738 .

https://www.ncbi.nlm.nih.gov/pubmed/28512451

本文引用 [1]

[41]

Kim

, Paik

, Ramirez

, et al. Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4⁺ T cells[J]. Immunity, 2022, 55(1): 145-158.e7. PMCID: PMC8755621. DOI: 10.1016/j.immuni.2021.11.005 .

https://www.ncbi.nlm.nih.gov/pubmed/34879222

本文引用 [1]

[42]	Muhammad F, Fan B, Wang R, et al. The molecular gut-brain axis in early brain development[J]. Int J Mol Sci, 2022, 23(23): 15389. PMCID: PMC9739658. DOI: 10.3390/ijms232315389 . https://www.ncbi.nlm.nih.gov/pubmed/36499716 本文引用 [1]

[43]	DeSocio JE. Epigenetics, maternal prenatal psychosocial stress, and infant mental health[J]. Arch Psychiatr Nurs, 2018, 32(6): 901-906. DOI: 10.1016/j.apnu.2018.09.001 . https://www.ncbi.nlm.nih.gov/pubmed/30454636 本文引用 [1]

[44]

Jones

, Acevedo

, Avalos

, et al. Association between maternal perceived stress during pregnancy and offspring DNA methylation changes in HPA axis genes at birth in the ECHO consortium[J]. Environ Epigenet, 2025, 11(1): dvaf024. PMCID: PMC12462613. DOI: 10.1093/eep/dvaf024 .

https://www.ncbi.nlm.nih.gov/pubmed/41020071

本文引用 [1]

[45]

Zheng

, Fan

, Zhang

, et al. Gestational stress induces depressive-like and anxiety-like phenotypes through epigenetic regulation of BDNF expression in offspring hippocampus[J]. Epigenetics, 2016, 11(2): 150-162. PMCID: PMC4846107. DOI: 10.1080/15592294.2016.1146850 .

https://www.ncbi.nlm.nih.gov/pubmed/26890656

本文引用 [1]

[46]	Woo T, King C, Ahmed NI, et al. microRNA as a maternal marker for prenatal stress-associated ASD, evidence from a murine model[J]. J Pers Med, 2023, 13(9): 1412. PMCID: PMC10533003. DOI: 10.3390/jpm13091412 . https://www.ncbi.nlm.nih.gov/pubmed/37763179 本文引用 [1]

[47]	Lautarescu A, Craig MC, Glover V. Prenatal stress: effects on fetal and child brain development[J]. Int Rev Neurobiol, 2020, 150: 17-40. DOI: 10.1016/bs.irn.2019.11.002 . https://www.ncbi.nlm.nih.gov/pubmed/32204831 本文引用 [1]

[48]	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. PMCID: PMC3897394. DOI: 10.1016/j.cell.2013.11.024 . https://www.ncbi.nlm.nih.gov/pubmed/24315484 本文引用 [2]

[49]	Lin TL, Lu CC, Chen TW, et al. Amelioration of maternal immune activation-induced autism relevant behaviors by gut commensal Parabacteroides goldsteinii [J]. Int J Mol Sci, 2022, 23(21): 13070. PMCID: PMC9657948. DOI: 10.3390/ijms232113070 . https://www.ncbi.nlm.nih.gov/pubmed/36361859 本文引用 [1]

[50]

Liu

, Liong

, Chung

, et al. Effects of Lactobacillus plantarum PS128 on children with autism spectrum disorder in Taiwan: a randomized, double-blind, placebo-controlled trial[J]. Nutrients, 2019, 11(4): 820. PMCID: PMC6521002. DOI: 10.3390/nu11040820 .

https://www.ncbi.nlm.nih.gov/pubmed/30979038

本文引用 [1]

[51]

Chen

, Wu

, Kim

, et al. Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of Lactiplantibacillus plantarum intervention[J]. Gut Microbes, 2024, 16(1): 2359501. PMCID: PMC11164232. DOI: 10.1080/19490976.2024.2359501 .

https://www.ncbi.nlm.nih.gov/pubmed/38841895

本文引用 [1]

[52]	Dooling SW, Sgritta M, Wang IC, et al. The effect of limosilactobacillus reuteri on social behavior is independent of the adaptive immune system[J]. mSystems, 2022, 7(6): e0035822. PMCID: PMC9765170. DOI: 10.1128/msystems.00358-22 . https://www.ncbi.nlm.nih.gov/pubmed/36286493 本文引用 [1]

[53]	Danhof HA, Lee J, Thapa A, et al. Microbial stimulation of oxytocin release from the intestinal epithelium via secretin signaling[J]. Gut Microbes, 2023, 15(2): 2256043. PMCID: PMC10498800. DOI: 10.1080/19490976.2023.2256043 . https://www.ncbi.nlm.nih.gov/pubmed/37698879

[54]

Mazzone

, Dooling

, Volpe

, 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. DOI: 10.1016/j.chom.2023.11.021 .

https://www.ncbi.nlm.nih.gov/pubmed/38113884

本文引用 [2]

[55]

Sgritta

, Dooling

, Buffington

, 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. PMCID: PMC6645363. DOI: 10.1016/j.neuron.2018.11.018 .

https://www.ncbi.nlm.nih.gov/pubmed/30522820

本文引用 [1]

[56]	Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication[J]. Front Endocrinol (Lausanne), 2020, 11: 25. PMCID: PMC7005631. DOI: 10.3389/fendo.2020.00025 . https://www.ncbi.nlm.nih.gov/pubmed/32082260 本文引用 [1]

[57]	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. PMCID: PMC10054498. DOI: 10.3390/nu15061415 . https://www.ncbi.nlm.nih.gov/pubmed/36986145 本文引用 [1]