Skip to main content
SpringerLink
Log in

Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals

  • Chapter
  • First Online:
Microorganisms and Mental Health

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 61))

Abstract

Autism Spectrum Disorder is a developmental condition associated with impairments in communication and social interactions, and repetitive and restricted behavior or interests. Autistic individuals are more likely to experience gastrointestinal (GI) symptoms than neurotypical individuals. This may be partially due to dysbiosis of the gut microbiome. In this article, we describe the interaction of the microbiome and immune system on autism etiology. We also summarize the links between the microbiome and gastrointestinal and related symptoms among autistic individuals. We report that microbial interventions, including diet, probiotics, antibiotics, and fecal transplants, and immune-modulating therapies such as cytokine blockade during the preconception, pregnancy, and postnatal period may impact the neurodevelopment, behavior, and gastrointestinal health of autistic individuals.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 179.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abazyan B, Nomura J, Kannan G et al (2010) Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biol Psychiatry 68(12):1172–1181

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abrahams BS, Geschwind DH (2008) Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet 9(5):341–355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • American Psychiatric Association D, Association AP (2013) Diagnostic and statistical manual of mental disorders: DSM-5, vol 5. American Psychiatric Association, Washington

    Book  Google Scholar 

  • Ardalan M, Chumak T, Vexler Z, Mallard C (2019) Sex-dependent effects of perinatal inflammation on the brain: implication for neuro-psychiatric disorders. Int J Mol Sci 20(9):2270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Arnold LE, Luna RA, Williams K et al (2019) Probiotics for gastrointestinal symptoms and quality of life in autism: a placebo-controlled pilot trial. J Child Adolesc Psychopharmacol 29(9):659–669

    Article  PubMed  PubMed Central  Google Scholar 

  • Ashwood P, Krakowiak P, Hertz-Picciotto I, Hansen R, Pessah I, Van de Water J (2011) Elevated plasma cytokines in autism spectrum disorders provide evidence of immune dysfunction and are associated with impaired behavioral outcome. Brain Behav Immun 25(1):40–45

    Article  CAS  PubMed  Google Scholar 

  • Bacchelli E, Maestrini E (2006) Autism spectrum disorders: molecular genetic advances. Wiley Online Library, pp 13–23

    Google Scholar 

  • Baron-Cohen S, Lombardo MV, Auyeung B, Ashwin E, Chakrabarti B, Knickmeyer R (2011) Why are autism spectrum conditions more prevalent in males? PLoS Biol 9(6):e1001081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blessing EM, Murty VP, Zeng B, Wang J, Davachi L, Goff DC (2020) Anterior hippocampal–cortical functional connectivity distinguishes antipsychotic naïve first-episode psychosis patients from controls and may predict response to second-generation antipsychotic treatment. Schizophr Bull 46(3):680–689

    Article  PubMed  Google Scholar 

  • Brigida AL, Schultz S, Cascone M, Antonucci N, Siniscalco D (2017) Endocannabinod signal dysregulation in autism spectrum disorders: a correlation link between inflammatory state and neuro-immune alterations. Int J Mol Sci 18(7):1425

    Article  PubMed  PubMed Central  Google Scholar 

  • Careaga M, Murai T, Bauman MD (2017) Maternal immune activation and autism spectrum disorder: from rodents to nonhuman and human primates. Biol Psychiatry 81(5):391–401

    Article  CAS  PubMed  Google Scholar 

  • Careaga M, Taylor SL, Chang C et al (2018) Variability in PolyIC induced immune response: implications for preclinical maternal immune activation models. J Neuroimmunol 323:87–93

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chakraborty P, Carpenter KL, Major S et al (2021) Gastrointestinal problems are associated with increased repetitive behaviors but not social communication difficulties in young children with autism spectrum disorders. Autism 25(2):405–415

    Article  PubMed  Google Scholar 

  • Chaste P, Leboyer M (2022) Autism risk factors: genes, environment, and gene-environment interactions. Dialogues Clin Neurosci

    Google Scholar 

  • Choi GB, Yim YS, Wong H et al (2016) The maternal interleukin-17a pathway in mice promotes autism-like phenotypes in offspring. Science 351(6276):933–939

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Comer AL, Carrier M, Tremblay M-È, Cruz-Martín A (2020) The inflamed brain in schizophrenia: the convergence of genetic and environmental risk factors that lead to uncontrolled neuroinflammation. Front Cell Neurosci 274

    Google Scholar 

  • Critchfield JW, Van Hemert S, Ash M, Mulder L, Ashwood P (2011) The potential role of probiotics in the management of childhood autism spectrum disorders. Gastroenterol Res Pract 2011

    Google Scholar 

  • Croen LA, Zerbo O, Qian Y et al (2015) The health status of adults on the autism spectrum. Autism 19(7):814–823

    Article  PubMed  Google Scholar 

  • Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M (2002) Activation of the inflammatory response system in autism. Neuropsychobiology 45(1):1–6

    Article  CAS  PubMed  Google Scholar 

  • Daliri EB-M, Tango CN, Lee BH, Oh D-H (2018) Human microbiome restoration and safety. Int J Med Microbiol 308(5):487–497

    Article  PubMed  Google Scholar 

  • Davies C, Mishra D, Eshraghi RS et al (2021) Altering the gut microbiome to potentially modulate behavioral manifestations in autism spectrum disorders: a systematic review. Neurosci Biobehav Rev 128:549–557

    Article  CAS  PubMed  Google Scholar 

  • Doenyas C (2018) Gut microbiota, inflammation, and probiotics on neural development in autism spectrum disorder. Neuroscience 374:271–286

    Article  CAS  PubMed  Google Scholar 

  • Emanuele E, Orsi P, Boso M et al (2010) Low-grade endotoxemia in patients with severe autism. Neurosci Lett 471(3):162–165

    Article  CAS  PubMed  Google Scholar 

  • Estes ML, McAllister AK (2015) Immune mediators in the brain and peripheral tissues in autism spectrum disorder. Nat Rev Neurosci 16(8):469–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Estes ML, McAllister AK (2016) Maternal immune activation: implications for neuropsychiatric disorders. Science 353(6301):772–777

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fatemi SH, Sidwell R, Akhter P et al (1998a) Human influenza viral infection in utero increases nNOS expression in hippocampi of neonatal mice. Synapse 29(1):84–88

    Article  CAS  PubMed  Google Scholar 

  • Fatemi SH, Sidwell R, Kist D et al (1998b) Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero. Brain Res 800(1):1–9

    Article  CAS  PubMed  Google Scholar 

  • Fatemi SH, Cuadra AE, El-Fakahany EE, Sidwell RW, Thuras P (2000) Prenatal viral infection causes alterations in nNOS expression in developing mouse brains. Neuroreport 11(7):1493–1496

    Article  CAS  PubMed  Google Scholar 

  • Fatemi SH, Earle J, Kanodia R et al (2002) Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol 22(1):25–33

    Article  PubMed  Google Scholar 

  • Foley KA, MacFabe DF, Vaz A, Ossenkopp K-P, Kavaliers M (2014) Sexually dimorphic effects of prenatal exposure to propionic acid and lipopolysaccharide on social behavior in neonatal, adolescent, and adult rats: implications for autism spectrum disorders. Int J Dev Neurosci 39:68–78

    Article  CAS  PubMed  Google Scholar 

  • Fox-Edmiston E, Van de Water J (2015) Maternal anti-fetal brain IgG autoantibodies and autism spectrum disorder: current knowledge and its implications for potential therapeutics. CNS Drugs 29(9):715–724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Frye RE, Melnyk S, MacFabe DF (2013) Unique acyl-carnitine profiles are potential biomarkers for acquired mitochondrial disease in autism spectrum disorder. Transl Psychiatry 3(1):e220–e220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gebrayel P, Nicco C, Al Khodor S et al (2022) Microbiota medicine: towards clinical revolution. J Transl Med 20(1):1–20

    Article  Google Scholar 

  • Gilmore JH, Jarskog LF, Vadlamudi S (2005) Maternal poly I: C exposure during pregnancy regulates TNFα, BDNF, and NGF expression in neonatal brain and the maternal–fetal unit of the rat. J Neuroimmunol 159(1–2):106–112

    Article  CAS  PubMed  Google Scholar 

  • GÅ‚adysz D, KrzywdziÅ„ska A, Hozyasz KK (2018) Immune abnormalities in autism spectrum disorder – could they hold promise for causative treatment? Mol Neurobiol 55(8):6387–6435

    Article  PubMed  PubMed Central  Google Scholar 

  • Grimaldi R, Gibson GR, Vulevic J et al (2018) A prebiotic intervention study in children with autism spectrum disorders (ASDs). Microbiome 6(1):1–13

    Article  Google Scholar 

  • Haida O, Al Sagheer T, Balbous A et al (2019) Sex-dependent behavioral deficits and neuropathology in a maternal immune activation model of autism. Transl Psychiatry 9(1):1–12

    Article  CAS  Google Scholar 

  • Harrington V, Lau L, Seddu K, Suez J (2021) Ecology and medicine converge at the microbiome-host interface. Msystems 6(4):e00756–e00721

    Article  CAS  Google Scholar 

  • Harvey L, Boksa P (2012) Prenatal and postnatal animal models of immune activation: relevance to a range of neurodevelopmental disorders. Dev Neurobiol 72(10):1335–1348

    Article  CAS  PubMed  Google Scholar 

  • Heberling CA, Dhurjati PS, Sasser M (2013) Hypothesis for a systems connectivity model of autism spectrum disorder pathogenesis: links to gut bacteria, oxidative stress, and intestinal permeability. Med Hypotheses 80(3):264–270

    Article  PubMed  Google Scholar 

  • Ho LKH, Tong VJW, Syn N et al (2020) Gut microbiota changes in children with autism spectrum disorder: a systematic review. Gut Pathogens 12(1):1–18

    Article  Google Scholar 

  • Holingue C, Newill C, Lee LC, Pasricha PJ, Daniele FM (2018) Gastrointestinal symptoms in autism spectrum disorder: a review of the literature on ascertainment and prevalence. Autism Res 11(1):24–36

    Article  PubMed  Google Scholar 

  • Holingue C, Budavari AC, Rodriguez KM, Zisman CR, Windheim G, Fallin MD (2020a) Sex differences in the gut-brain axis: implications for mental health. Curr Psychiatry Rep 22(12):83. https://doi.org/10.1007/s11920-020-01202-y

    Article  PubMed  PubMed Central  Google Scholar 

  • Holingue C, Brucato M, Ladd-Acosta C et al (2020b) Interaction between maternal immune activation and antibiotic use during pregnancy and child risk of autism spectrum disorder. Autism Res 13(12):2230–2241

    Article  PubMed  PubMed Central  Google Scholar 

  • Holingue C, Poku O, Pfeiffer D, Murray S, Fallin MD (2021) Gastrointestinal concerns in children with autism spectrum disorder: a qualitative study of family experiences. Autism:13623613211062667

    Google Scholar 

  • Hsiao EY, McBride SW, Hsien S et al (2013a) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155(7):1451–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hsiao EY, McBride SW, Hsien S et al (2013b) The microbiota modulates gut physiology and behavioral abnormalities associated with autism. Cell 155(7):1451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hullar MA, Fu BC (2014) Diet, the gut microbiome, and epigenetics. Cancer J 20(3):170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inga Jácome MC, Morales Chacòn LM, Vera Cuesta H et al (2016) Peripheral inflammatory markers contributing to comorbidities in autism. Behav Sci 6(4):29

    Article  PubMed  PubMed Central  Google Scholar 

  • Inoue D, Kimura I, Wakabayashi M et al (2012) Short-chain fatty acid receptor GPR41-mediated activation of sympathetic neurons involves synapsin 2b phosphorylation. FEBS Lett 586(10):1547–1554

    Article  CAS  PubMed  Google Scholar 

  • Inoue R, Sakaue Y, Kawada Y et al (2019) Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder. J Clin Biochem Nutr 64(3):217–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ivanov II, Atarashi K, Manel N et al (2009) Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell 139(3):485–498

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaidanovich-Beilin O, Lipina T, Vukobradovic I, Roder J, Woodgett JR (2011) Assessment of social interaction behaviors. J Vis Exp (48):e2473

    Google Scholar 

  • Kang D-W, Adams JB, Gregory AC et al (2017) Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome 5(1):1–16

    Article  Google Scholar 

  • Kang D-W, Adams JB, Coleman DM et al (2019) Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota. Sci Rep 9(1):1–9

    Google Scholar 

  • Kentner AC, Bilbo SD, Brown AS et al (2019) Maternal immune activation: reporting guidelines to improve the rigor, reproducibility, and transparency of the model. Neuropsychopharmacology 44(2):245–258

    Article  PubMed  Google Scholar 

  • Kim S, Kim H, Yim YS et al (2017) Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring. Nature 549(7673):528–532

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim YS, Unno T, Kim B-Y, Park M-S (2020) Sex differences in gut microbiota. World J Men’s Health 38(1):48–60

    Article  Google Scholar 

  • Kim E, Paik D, Ramirez RN et al (2022) Maternal gut bacteria drive intestinal inflammation in offspring with neurodevelopmental disorders by altering the chromatin landscape of CD4+ T cells. Immunity 55(1):145–158.e7

    Article  CAS  PubMed  Google Scholar 

  • Kong X, Liu J, Cetinbas M et al (2019) New and preliminary evidence on altered oral and gut microbiota in individuals with autism spectrum disorder (ASD): implications for ASD diagnosis and subtyping based on microbial biomarkers. Nutrients 11(9):2128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kowash H, Potter H, Edye M et al (2019) Poly (I: C) source, molecular weight and endotoxin contamination affect dam and prenatal outcomes, implications for models of maternal immune activation. Brain Behav Immun 82:160–166

    Article  CAS  PubMed  Google Scholar 

  • Lai M-C, Kassee C, Besney R et al (2019) Prevalence of co-occurring mental health diagnoses in the autism population: a systematic review and meta-analysis. Lancet Psychiatry 6(10):819–829

    Article  PubMed  Google Scholar 

  • Lammert CR, Frost EL, Bolte AC et al (2018) Cutting edge: critical roles for microbiota-mediated regulation of the immune system in a prenatal immune activation model of autism. J Immunol 201(3):845–850

    Article  CAS  PubMed  Google Scholar 

  • Lipina TV, Zai C, Hlousek D, Roder JC, Wong AH (2013) Maternal immune activation during gestation interacts with Disc1 point mutation to exacerbate schizophrenia-related behaviors in mice. J Neurosci 33(18):7654–7666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H (2019) Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Transl Psychiatry 9(1):1–13

    Article  Google Scholar 

  • Lyall K, Croen L, Daniels J et al (2017) The changing epidemiology of autism spectrum disorders. Annu Rev Public Health 38:81–102

    Article  PubMed  Google Scholar 

  • MacFabe DF (2012) Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microb Ecol Health Dis 23(1):19260

    Google Scholar 

  • MacFabe D (2013) Autism: metabolism, mitochondria, and the microbiome. Global Adv Health Med 2(6):52–66

    Article  Google Scholar 

  • Madra M, Ringel R, Margolis KG (2020) Gastrointestinal issues and autism spectrum disorder. Child Adolesc Psychiatr Clin N Am 29(3):501–513

    Article  PubMed  PubMed Central  Google Scholar 

  • Maenner MJ, Shaw KA, Bakian AV et al (2021) Prevalence and characteristics of autism spectrum disorder among children aged 8 years – autism and developmental disabilities monitoring network, 11 sites, United States, 2018. MMWR Surveill Summ 70(11):1

    Article  PubMed  PubMed Central  Google Scholar 

  • Malkova NV, Collin ZY, Hsiao EY, Moore MJ, Patterson PH (2012) Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism. Brain Behav Immun 26(4):607–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Marler S, Ferguson BJ, Lee EB et al (2017) Association of rigid-compulsive behavior with functional constipation in autism spectrum disorder. J Autism Dev Disord 47(6):1673–1681

    Article  PubMed  PubMed Central  Google Scholar 

  • Masi A, Quintana D, Glozier N, Lloyd A, Hickie I, Guastella A (2015) Cytokine aberrations in autism spectrum disorder: a systematic review and meta-analysis. Mol Psychiatry 20(4):440–446

    Article  CAS  PubMed  Google Scholar 

  • Mazina V, Gerdts J, Trinh S et al (2015) Epigenetics of autism-related impairment: copy number variation and maternal infection. J Dev Behav Pediatr 36(2):61–67

    Article  PubMed  PubMed Central  Google Scholar 

  • Mazmanian SK, Round JL, Kasper DL (2008) A microbial symbiosis factor prevents intestinal inflammatory disease. Nature 453(7195):620–625

    Article  CAS  PubMed  Google Scholar 

  • Mead J, Ashwood P (2015) Evidence supporting an altered immune response in ASD. Immunol Lett 163(1):49–55

    Article  CAS  PubMed  Google Scholar 

  • Meltzer A, Van de Water J (2017) The role of the immune system in autism spectrum disorder. Neuropsychopharmacology 42(1):284–298

    Article  CAS  PubMed  Google Scholar 

  • Meyer U (2014) Prenatal poly (i: C) exposure and other developmental immune activation models in rodent systems. Biol Psychiatry 75(4):307–315

    Article  CAS  PubMed  Google Scholar 

  • Meyer U (2019) Neurodevelopmental resilience and susceptibility to maternal immune activation. Trends Neurosci 42(11):793–806

    Article  CAS  PubMed  Google Scholar 

  • Meyer U, Feldon J, Schedlowski M, Yee BK (2005) Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia. Neurosci Biobehav Rev 29(6):913–947

    Article  CAS  PubMed  Google Scholar 

  • Meyer U, Feldon J, Dammann O (2011) Schizophrenia and autism: both shared and disorder-specific pathogenesis via perinatal inflammation? Pediatr Res 69(8):26–33

    Article  Google Scholar 

  • Morais LH, Felice D, Golubeva AV, Moloney G, Dinan TG, Cryan JF (2018) Strain differences in the susceptibility to the gut–brain axis and neurobehavioural alterations induced by maternal immune activation in mice. Behav Pharmacol 29(2):181–198

    Article  CAS  PubMed  Google Scholar 

  • Mostafa GA, Al-Ayadhi LY (2011) Increased serum levels of anti-ganglioside M1 auto-antibodies in autistic children: relation to the disease severity. J Neuroinflammation 8(1):1–6

    Article  Google Scholar 

  • Nardone S, Elliott E (2016) The interaction between the immune system and epigenetics in the etiology of autism spectrum disorders. Front Neurosci 329

    Google Scholar 

  • Nestler EJ, Hyman SE (2010) Animal models of neuropsychiatric disorders. Nat Neurosci 13(10):1161–1169

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Newschaffer CJ, Fallin D, Lee NL (2002) Heritable and nonheritable risk factors for autism spectrum disorders. Epidemiol Rev 24(2):137–153

    Article  PubMed  Google Scholar 

  • Newschaffer CJ, Croen LA, Daniels J et al (2007) The epidemiology of autism spectrum disorders. Annu Rev Public Health 28:235–258. https://doi.org/10.1146/annurev.publhealth.28.021406.144007

    Article  PubMed  Google Scholar 

  • Ochoa-Repáraz J, Mielcarz DW, Ditrio LE et al (2010) Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide a expression. J Immunol 185(7):4101–4108

    Article  PubMed  Google Scholar 

  • Onore C, Careaga M, Ashwood P (2012) The role of immune dysfunction in the pathophysiology of autism. Brain Behav Immun 26(3):383–392

    Article  CAS  PubMed  Google Scholar 

  • Osokine I, Erlebacher A (2017) Inflammation and autism: from maternal gut to fetal brain. Trends Mol Med 23(12):1070–1071

    Article  PubMed  Google Scholar 

  • Patterson PH (2009) Immune involvement in schizophrenia and autism: etiology, pathology and animal models. Behav Brain Res 204(2):313–321

    Article  CAS  PubMed  Google Scholar 

  • Patterson PH (2011) Maternal infection and immune involvement in autism. Trends Mol Med 17(7):389–394

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Paysour MJ, Bolte AC, Lukens JR (2019) Crosstalk between the microbiome and gestational immunity in autism-related disorders. DNA Cell Biol 38(5):405–409

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reigstad CS, Salmonson CE, Rainey JF III et al (2015) Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J 29(4):1395–1403

    Article  CAS  PubMed  Google Scholar 

  • Ruskin DN, Murphy MI, Slade SL, Masino SA (2017) Ketogenic diet improves behaviors in a maternal immune activation model of autism spectrum disorder. PLoS One 12(2):e0171643

    Article  PubMed  PubMed Central  Google Scholar 

  • Sampson TR, Mazmanian SK (2015) Control of brain development, function, and behavior by the microbiome. Cell Host Microbe 17(5):565–576

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sanctuary MR, Kain JN, Chen SY et al (2019) Pilot study of probiotic/colostrum supplementation on gut function in children with autism and gastrointestinal symptoms. PLoS One 14(1):e0210064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sandin S, Lichtenstein P, Kuja-Halkola R, Hultman C, Larsson H, Reichenberg A (2017) The heritability of autism spectrum disorder. JAMA 318(12):1182–1184

    Article  PubMed  PubMed Central  Google Scholar 

  • Saurman V, Margolis KG, Luna RA (2020) Autism spectrum disorder as a brain-gut-microbiome axis disorder. Dig Dis Sci 65(3):818–828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schmidt RJ, Hansen RL, Hartiala J et al (2011) Prenatal vitamins, one-carbon metabolism gene variants, and risk for autism. Epidemiology 22(4):476

    Article  PubMed  PubMed Central  Google Scholar 

  • Schwartzer J, Careaga M, Onore C, Rushakoff J, Berman RF, Ashwood P (2013) Maternal immune activation and strain specific interactions in the development of autism-like behaviors in mice. Transl Psychiatry 3(3):e240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharon G, Sampson TR, Geschwind DH, Mazmanian SK (2016) The central nervous system and the gut microbiome. Cell 167(4):915–932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23(1):297–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH (2009) Activation of the maternal immune system alters cerebellar development in the offspring. Brain Behav Immun 23(1):116–123

    Article  PubMed  Google Scholar 

  • Shin Yim Y, Park A, Berrios J et al (2017) Reversing behavioural abnormalities in mice exposed to maternal inflammation. Nature 549(7673):482–487

    Article  PubMed  Google Scholar 

  • Silverman JL, Yang M, Lord C, Crawley JN (2010) Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci 11(7):490–502

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Siniscalco D, Schultz S, Brigida AL, Antonucci N (2018) Inflammation and neuro-immune dysregulations in autism spectrum disorders. Pharmaceuticals 11(2):56

    Article  PubMed  PubMed Central  Google Scholar 

  • Sivan A, Corrales L, Hubert N et al (2015) Commensal bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 350(6264):1084–1089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Slattery J, MacFabe DF, Frye RE (2016) The significance of the enteric microbiome on the development of childhood disease: a review of prebiotic and probiotic therapies in disorders of childhood. Clin Med Insights Pediatr 10:91–107. https://doi.org/10.4137/CMPed.S38338

    Article  PubMed  PubMed Central  Google Scholar 

  • Strati F, Cavalieri D, Albanese D et al (2017) New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome 5(1):1–11

    Article  Google Scholar 

  • Supekar K, Uddin LQ, Khouzam A et al (2013) Brain hyperconnectivity in children with autism and its links to social deficits. Cell Rep 5(3):738–747

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tanabe S, Kinuta Y, Saito Y (2008) Bifidobacterium infantis suppresses proinflammatory interleukin-17 production in murine splenocytes and dextran sodium sulfate-induced intestinal inflammation. Int J Mol Med 22(2):181–185

    CAS  PubMed  Google Scholar 

  • Tordjman S, Drapier D, Bonnot O et al (2007) Animal models relevant to schizophrenia and autism: validity and limitations. Behav Genet 37(1):61–78

    Article  PubMed  Google Scholar 

  • Tsukada T, Shimada H, Sakata-Haga H, Iizuka H, Hatta T (2019) Molecular mechanisms underlying the models of neurodevelopmental disorders in maternal immune activation relevant to the placenta. Congenit Anom 59(3):81–87

    Article  Google Scholar 

  • Tye C, Runicles AK, Whitehouse AJ, Alvares GA (2019) Characterizing the interplay between autism spectrum disorder and comorbid medical conditions: an integrative review. Front Psych 751

    Google Scholar 

  • Urakubo A, Jarskog LF, Lieberman JA, Gilmore JH (2001) Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. Schizophr Res 47(1):27–36

    Article  CAS  PubMed  Google Scholar 

  • Vita A, De Peri L, Deste G, Sacchetti E (2012) Progressive loss of cortical gray matter in schizophrenia: a meta-analysis and meta-regression of longitudinal MRI studies. Transl Psychiatry 2(11):e190–e190

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Volk HE, Kerin T, Lurmann F, Hertz-Picciotto I, McConnell R, Campbell DB (2014) Brief report: autism spectrum disorder: interaction of air pollution with the MET receptor tyrosine kinase gene. Epidemiology:44–47

    Google Scholar 

  • Vuillermot S, Luan W, Meyer U, Eyles D (2017) Vitamin D treatment during pregnancy prevents autism-related phenotypes in a mouse model of maternal immune activation. Mol Autism 8(1):1–13

    Article  Google Scholar 

  • Vuong HE, Hsiao EY (2017) Emerging roles for the gut microbiome in autism spectrum disorder. Biol Psychiatry 81(5):411–423

    Article  PubMed  Google Scholar 

  • Wang X, Yang J, Zhang H, Yu J, Yao Z (2019) Oral probiotic administration during pregnancy prevents autism-related behaviors in offspring induced by maternal immune activation via anti-inflammation in mice. Autism Res 12(4):576–588

    Article  PubMed  Google Scholar 

  • Wilke CM, Bishop K, Fox D, Zou W (2011) Deciphering the role of Th17 cells in human disease. Trends Immunol 32(12):603–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Willner P (1984) The validity of animal models of depression. Psychopharmacology (Berl) 83(1):1–16

    Article  CAS  PubMed  Google Scholar 

  • Xu G, Strathearn L, Liu B et al (2019) Prevalence and treatment patterns of autism spectrum disorder in the United States, 2016. JAMA Pediatr 173(2):153–159

    Article  PubMed  Google Scholar 

  • Xuan IC, Hampson DR (2014) Gender-dependent effects of maternal immune activation on the behavior of mouse offspring. PLoS One 9(8):e104433

    Article  PubMed  PubMed Central  Google Scholar 

  • Yano JM, Yu K, Donaldson GP et al (2015) Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161(2):264–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yap CX, Henders AK, Alvares GA et al (2021) Autism-related dietary preferences mediate autism-gut microbiome associations. Cell 184(24):5916–5931.e17

    Article  CAS  PubMed  Google Scholar 

  • Zuckerman L, Weiner I (2005) Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 39(3):311–323

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Amanda Kim & Calliope Holingue

  2. Department of Psychology, Pennsylvania State University, University Park, PA, USA

    Corina R. Zisman

  3. Center for Autism and Related Disorders, Kennedy Krieger Institute, Baltimore, MD, USA

    Calliope Holingue

Authors
  1. Amanda Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Corina R. Zisman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Calliope Holingue
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Calliope Holingue .

Editor information

Editors and Affiliations

  1. Laureate Inst for Brain Research, Tulsa, OK, USA

    Jonathan Savitz

  2. Psychiatry and Behavioral Sciences Dept, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Robert H. Yolken

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Kim, A., Zisman, C.R., Holingue, C. (2022). Influences of the Immune System and Microbiome on the Etiology of ASD and GI Symptomology of Autistic Individuals. In: Savitz, J., Yolken, R.H. (eds) Microorganisms and Mental Health. Current Topics in Behavioral Neurosciences, vol 61. Springer, Cham. https://doi.org/10.1007/7854_2022_371

Download citation

Publish with us

Policies and ethics

Search

Navigation