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Autism and neuro-immune-gut link

1 Department of Experimental Medicine, University of Campania, 80138 Napoli, Italy
2 Italian Group for Studying Autism – GISA – 25018 Brescia, Italy
3 Biomedical Center for Autism Research and Treatment – 70124 Bari, Italy

Special Issues: 2nd European Conference of Biomedical Research and Treatments for Autism

Recent evidences sustain the hypothesis that host-bacteria interactions play a critical role in regulating tissue and body homeostasis. Gut microbiota and the brain are strongly interconnected and share communication pathways. Modifications in gut bacteria compositions are correlated to changes in behaviors. Indeed, autism spectrum disorders (ASD) are linked to dysfunctions of the gut bacteria-brain axis. Possible therapeutic strategies in ASD management will aim to restore dysbiosis and gut bacteria imbalance.
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Keywords autism; gut brain axis; intestinal dysfunctions; neuroinflammation

Citation: Dario Siniscalco, Anna Lisa Brigida, Nicola Antonucci. Autism and neuro-immune-gut link. AIMS Molecular Science, 2018, 5(2): 166-172. doi: 10.3934/molsci.2018.2.166


  • 1. Blikslager AT, Moeser AJ, Gookin JL, et al. (2007) Restoration of barrier function in injured intestinal mucosa. Physiol Rev 87: 545.    
  • 2. Podolsky DK (1999) V. Innate mechanisms of mucosal defense and repair: The best offense is a good defense. Am J Physiol 277: G495–G499.
  • 3. Kunzelmann K, Mall M (2002) Electrolyte transport in the mammalian colon: Mechanisms and Implications for disease. Physiol Rev 82: 245–289.    
  • 4. Ferraris RP, Diamond J (1997) Regulation of intestinal sugar transport. Physiol Rev 77: 257–302.    
  • 5. Groschwitz KR, Hogan SP (2009) Intestinal barrier function: Molecular regulation and disease pathogenesis. J Allergy Clin Immunol 124: 3–22.    
  • 6. Bischoff S, Barbara G, Buurman W, et al. (2014) Intestinal permeability-A new target for disease prevention and therapy. BMC Gastroenterol 14: 189–214.    
  • 7. Van Itallie CM, Holmes J, Bridges A, et al. (2008) The density of small tight junction pores varies among cell types and is increased by expression of claudin-2. J Cell Sci 121: 298–305.    
  • 8. Ulluwishewa D, Anderson RC, Mcnabb WC, et al. (2011) Regulation of tight junction permeability by intestinal bacteria and dietary components. J Nutr 141: 769–776.    
  • 9. De Magistris L, Picardi A, Sapone A, et al. (2014) Intestinal barrier in autism, In: Patel VB (ed.), Comprehensive guide to autism, New York: Springer, 123.
  • 10. Catassi C, Fasano A (2008) Celiac disease. Curr Opin Gastroenterol 24: 687–691.    
  • 11. Bjarnason I, Macpherson A, Hollander D (1995) Intestinal permeability: An overview. Gastroenterology 108: 1566–1581.    
  • 12. Fasano A (2011) Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity and cancer. Physiol Rev 91: 151–175.    
  • 13. Lerner A, Matthias T (2015) Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease. Autoimmun Rev 14: 479–489.    
  • 14. Siniscalco D, Cirillo A, Bradstreet JJ, et al. (2013) Epigenetic findings in autism: New perspectives for therapy. Int J Environ Res Public Health 10: 4261–4273.    
  • 15. Siniscalco D, Antonucci N (2013) Possible use of Trichuris suis ova in autism spectrum disorders therapy. Med Hypotheses 81: 1–4.    
  • 16. Wakefield AJ (2002) The gut-brain axis in childhood developmental disorders. J Pediatr Gastroenterol Nutr 34: S14–S17.    
  • 17. Siniscalco D (2014) Gut bacteria-brain axis in autism. Autism 4: e124.
  • 18. Siniscalco D, Antonucci N (2013) Involvement of dietary bioactive proteins and peptides in autism spectrum disorders. Curr Protein Pept Sci 14: 674–679.
  • 19. Trivedi MS, Shah JS, Al-Mughairy S, et al. (2014) Food-derived opioid peptides inhibit cysteine uptake with redox and epigenetic consequences. J Nutr Biochem 25: 1011–1018.    
  • 20. Frustaci A, Neri M, Cesario A, et al. (2012) Oxidative stress-related biomarkers in autism: Systematic review and meta-analyses. Free Radic Biol Med 52: 2128–2141.    
  • 21. Melnyk S, Fuchs GJ, Schulz E, et al. (2012) Metabolic imbalance associated with methylation dys-regulation and oxidative damage in children with autism. J Autism Dev Disord 42: 367–377.    
  • 22. Shattock P, Whiteley P (2002) Biochemical aspects in autism spectrum disorders: Updating the opioid-excess theory and presenting new opportunities for biomedical intervention. Expert Opin Ther Targets 6: 175–183.    
  • 23. Siniscalco D, Sapone A, Giordano C, et al. (2013) Cannabinoid receptor type 2, but not type 1, is up-regulated in peripheral blood mononuclear cells of children affected by autistic disorders. J Autism Dev Disord 43: 2686–2695.    
  • 24. Siniscalco D, Bradstreet JJ, Cirillo A, et al. (2014) The in vitro GcMAF effects on endocannabinoid system transcriptionomics, receptor formation, and cell activity of autism-derived macrophages. J Neuroinflammation 11: 78.    
  • 25. Fiorentino M, Sapone A, Senger S, et al. (2016) Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders. Mol Autism 7: 49.    
  • 26. Rose DR, Yang H, Serena G, et al. (2018) Differential immune responses and microbiota profiles in children with autism spectrum disorders and co-morbid gastrointestinal symptoms. Brain Behav Immun 70: 354–368.    
  • 27. Lionetti E, Leonardi S, Franzonello C, et al. (2015) Gluten psychosis: Confirmation of a new clinical entity. Nutrients 7: 5532–5539.    
  • 28. O'Mahony SM, Clarke G, Borre YE, et al. (2015) Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. Behav Brain Res 277: 32–48.    
  • 29. Theije CGMD, Koelink PJ, Korte-Bouws GA, et al. (2014) Intestinal inflammation in a murine model of autism spectrum disorders. Brain Behav Immun 37: 240–247.    
  • 30. Baganz NL, Blakely RD (2013) A dialogue between the immune system and brain, spoken in the language of serotonin. ACS Chem Neurosci 4: 48–63.    
  • 31. Van Elst K, Bruining H, Birtoli B, et al. (2014) Food for thought: Dietary changes in essential fatty acid ratios and the increase in autism spectrum disorders. Neurosci Biobehav Rev 45: 369–738.    
  • 32. Halliwell B (2006) Oxidative stress and neurodegeneration: Where are we now? J Neurochem 97: 1634–1658.    
  • 33. Cartocci V, Catallo M, Tempestilli M, et al. (2018) Altered brain cholesterol/isoprenoid metabolism in a rat model of autism spectrum disorders. Neuroscience 372: 27–37.    
  • 34. Brigida AL, Schultz S, Cascone M, et al. (2017) Endocannabinod signal dysregulation in autism spectrum disorders: A correlation link between inflammatory state and neuro-immune alterations. Int J Mol Sci 18: 1425.    
  • 35. Acharya N, Penukonda S, Shcheglova T, et al. (2017) Endocannabinoid system acts as a regulator of immune homeostasis in the gut. Proc Natl Acad Sci USA 114: 5005–5010.    
  • 36. Gyires K, Zádori ZS (2016) Role of cannabinoids in gastrointestinal mucosal defense and inflammation. Curr Neuropharmacol 14: 935–951.    
  • 37. Maríbauset S, Llopisgonzález A, Zazpe I, et al. (2016) Nutritional Impact of a Gluten-Free Casein-Free Diet in Children with Autism Spectrum Disorder. J Autism Dev Disord 46: 673–684.    
  • 38. Iovene MR, Bombace F, Maresca R, et al. (2017) Intestinal Dysbiosis and Yeast Isolation in Stool of Subjects with Autism Spectrum Disorders. Mycopathologia 182: 349–363.    
  • 39. Siniscalco D, Mijatovic T, Bosmans E, et al. (2016) Decreased Numbers of CD57 + CD3- Cells Identify Potential Innate Immune Differences in Patients with Autism Spectrum Disorder. Vivo 30: 83–89.
  • 40. de Theije CG, Wopereis H, Ramadan M, et al. (2014) Altered gut microbiota and activity in a murine model of autism spectrum disorders. Brain Behav Immun 37: 197–206.    
  • 41. Needham BD, Tang W, Wu WL (2018) Searching for the gut microbial contributing factors to social behavior in rodent models of autism spectrum disorder. Dev Neurobiol 78: 474–499.    
  • 42. Fung TC, Olson CA, Hsiao EY (2017) Interactions between the microbiota, immune and nervous systems in health and disease. Nat Neurosci 20: 145–155.    
  • 43. Santocchi E, Guiducci L, Fulceri F, et al. (2016) Gut to brain interaction in Autism Spectrum Disorders: A randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters. BMC Psychiatry 16: 183.    


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