The relationship between Autism Spectrum Disorder, Gut-Brain axis and Gut Microbiota

Year 2024, Volume: 1 Issue: 1, 1 - 11, 31.01.2024

Gülsüm Yitik Tonkaz , Bedia Sultan Önal , Ertuğrul Çakır

Abstract

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder in which symptoms such as difficulty in social interaction, communication problems, limited interests, and limited behavioral patterns are observed. The prevalence of ASD has been increasing over the years, but its etiology has not been fully elucidated. Gastrointestinal (GI) symptoms are a common comorbidity in children with ASD, but the underlying mechanisms are unknown. Many studies have shown alterations in the composition of the gut microbiota and their metabolic products in patients with ASD. The gut microbiota influences brain development and behaviors through the neuroendocrine, neuroimmune, and autonomic nervous systems. In addition, abnormal gut microbiota is associated with several diseases, such as obesity, diabetes, autoimmune diseases, neurodegenerative diseases, and psychiatric diseases (ASD, depression, anxiety disorder, etc.). In this review, we aim to provide information about the bidirectional interactions between the central nervous system and the gastrointestinal tract (the gut-brain axis), the possible roles of the gut-brain axis and gut microbiota in the etiology of autism spectrum disorder, and current hypotheses.

Keywords

Autism Spectrum Disorder, Gut-brain axis, Gut Microbiota

References

• Association AP. American Psychiatric Association DSM-5 Task Force.(2013). Diagnostic and statistical manual of mental disorders: DSM.5.
• Maenner MJ, Warren Z, Williams AR, Amoakohene E, Bakian AV, Bilder DA, 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. MMWR Surveill Summ. 2023;72(2):1-14.
• Al-Beltagi M, Saeed NK, Bediwy AS, Elbeltagi R, Alhawamdeh R. Role of gastrointestinal health in managing children with autism spectrum disorder. World J Clin Pediatr. 2023;12(4):171-96.
• Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, et al. 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. 2016;16(1):183.
• Grenham S, Clarke G, Cryan JF, Dinan TG. Brain–gut–microbe communication in health and disease. Frontiers in physiology. 2011;2:94.
• Sartor RB. Microbial influences in inflammatory bowel diseases. Gastroenterology. 2008;134(2):577-94.
• Mangiola F, Ianiro G, Franceschi F, Fagiuoli S, Gasbarrini G, Gasbarrini A. Gut microbiota in autism and mood disorders. World journal of gastroenterology. 2016;22(1):361.
• Góralczyk-Bińkowska A, Szmajda-Krygier D, Kozłowska E. The Microbiota-Gut-Brain Axis in Psychiatric Disorders. Int J Mol Sci. 2022;23(19).
• Chen Y, Zhou J, Wang L. Role and Mechanism of Gut Microbiota in Human Disease. Front Cell Infect Microbiol. 2021;11:625913.
• Rieder R, Wisniewski PJ, Alderman BL, Campbell SC. Microbes and mental health: A review. Brain, behavior, and immunity. 2017;66:9-17.
• Clarke G, Grenham S, Scully P, Fitzgerald P, Moloney R, Shanahan F, et al. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Molecular psychiatry. 2013;18(6):666-73.
• Heijtz RD, Wang S, Anuar F, Qian Y, Björkholm B, Samuelsson A, et al. Normal gut microbiota modulates brain development and behavior. Proceedings of the National Academy of Sciences. 2011;108(7):3047-52.
• Li Q, Han Y, Dy ABC, Hagerman RJ. The gut microbiota and autism spectrum disorders. Frontiers in cellular neuroscience. 2017:120.
• Konsman JP, Luheshi GN, Bluthé RM, Dantzer R. The vagus nerve mediates behavioural depression, but not fever, in response to peripheral immune signals; a functional anatomical analysis. European Journal of Neuroscience. 2000;12(12):4434-46.
• Goehler LE, Park SM, Opitz N, Lyte M, Gaykema RP. Campylobacter jejuni infection increases anxiety-like behavior in the holeboard: possible anatomical substrates for viscerosensory modulation of exploratory behavior. Brain, behavior, and immunity. 2008;22(3):354-66.
• Lyte M, Li W, Opitz N, Gaykema RP, Goehler LE. Induction of anxiety-like behavior in mice during the initial stages of infection with the agent of murine colonic hyperplasia Citrobacter rodentium. Physiology & behavior. 2006;89(3):350-7.
• Forsythe P, Kunze WA. Voices from within: gut microbes and the CNS. Cellular and molecular life sciences. 2013;70:55-69.
• Bouskra D, Brézillon C, Bérard M, Werts C, Varona R, Boneca IG, et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature. 2008;456(7221):507-10.
• Macfarlane S, Macfarlane GT. Regulation of short-chain fatty acid production. Proceedings of the Nutrition Society. 2003;62(1):67-72.
• Holmes E, Kinross J, Gibson GR, Burcelin R, Jia W, Pettersson S, et al. Therapeutic modulation of microbiota-host metabolic interactions. Science translational medicine. 2012;4(137):137rv6-rv6.
• Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, et al. Host-gut microbiota metabolic interactions. Science. 2012;336(6086):1262-7.
• MacFabe DF. Enteric short-chain fatty acids: microbial messengers of metabolism, mitochondria, and mind: implications in autism spectrum disorders. Microbial ecology in health and disease. 2015;26(1):28177.
• Schröcksnadel K, Wirleitner B, Winkler C, Fuchs D. Monitoring tryptophan metabolism in chronic immune activation. Clinica chimica acta. 2006;364(1-2):82-90.
• Kurnasov O, Jablonski L, Polanuyer B, Dorrestein P, Begley T, Osterman A. Aerobic tryptophan degradation pathway in bacteria: novel kynurenine formamidase. FEMS microbiology letters. 2003;227(2):219-27.
• Varma GS. Major Depresif Bozuklukta Nöroinflamatuvar Hipotez/Neuroinflammatory Hypothesis in Major Depressive Disorder. Psikiyatride Guncel Yaklasimlar. 2014;6(1):1.
• Desbonnet L, Garrett L, Clarke G, Kiely B, Cryan JF, Dinan T. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience. 2010;170(4):1179-88.
• Fiş NP, Berkem M. Nörotransmitter Sistemlerinin Gelişimi ve Psikopatolojiye Yansımaları. Klinik Psikofarmakoloji Bulteni. 2009;19: 312-321
• Barrett E, Ross RP, O’Toole PW, Fitzgerald GF, Stanton C. ’This article corrects: c-Aminobutyric acid production by culturable bacteria from the human intestine ‘. J Appl Microbiol. 2014;116:1384-6.
• Smith-Hicks CL. GABAergic dysfunction in pediatric neuro-developmental disorders. Frontiers in Cellular Neuroscience. 2013;7:269.
• Barrett E, Ross R, O'Toole PW, Fitzgerald GF, Stanton C. γ‐Aminobutyric acid production by culturable bacteria from the human intestine. Journal of applied microbiology. 2012;113(2):411-7.
• Bravo JA, Forsythe P, Chew MV, Escaravage E, Savignac HM, Dinan TG, et al. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve. Proceedings of the National Academy of Sciences. 2011;108(38):16050-5.
• Lam KS, Aman MG, Arnold LE. Neurochemical correlates of autistic disorder: a review of the literature. Research in developmental disabilities. 2006;27(3):254-89.
• Reigstad CS, Salmonson CE, Rainey III JF, Szurszewski JH, Linden DR, Sonnenburg JL, et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. The FASEB Journal. 2015;29(4):1395.
• Bercik P, Denou E, Collins J, Jackson W, Lu J, Jury J, et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology. 2011;141(2):599-609. e3.
• Hashimoto K, Shimizu E, Iyo M. Critical role of brain-derived neurotrophic factor in mood disorders. Brain research reviews. 2004;45(2):104-14.
• Bercik P, Verdu EF, Foster JA, Macri J, Potter M, Huang X, et al. Chronic gastrointestinal inflammation induces anxiety-like behavior and alters central nervous system biochemistry in mice. Gastroenterology. 2010;139(6):2102-12. e1.
• Esworthy RS, Smith DD, Chu F-F. “A Strong Impact of Genetic Background on Gut Microflora in Mice.” International journal of inflammation vol. 2010,2010 (2010): 986046. doi:10.4061/2010/986046
• Zhu J, Guo M, Yang T, Lai X, Lei Y, He M, et al. Association between behavioral problems and gastrointestinal disorders among children with autism spectrum disorder. Zhonghua er ke za zhi= Chinese Journal of Pediatrics. 2017;55(12):905-10.
• Heberling CA, Dhurjati PS, Sasser M. Hypothesis for a systems connectivity model of autism spectrum disorder pathogenesis: Links to gut bacteria, oxidative stress, and intestinal permeability. Medical hypotheses. 2013;80(3):264-70.
• Yalçın SS, KanatlıMÇ. İntestinal mikrobiyota transplantasyonu; neden, kime, nasıl? Pamukkale Medical Journal. 2015(2):148-54.
• Mayer EA, Padua D, Tillisch K. Altered brain‐gut axis in autism: comorbidity or causative mechanisms? Bioessays. 2014;36(10):933-9.
• Fattorusso A, Di Genova L, Dell’Isola GB, Mencaroni E, Esposito S. Autism spectrum disorders and the gut microbiota. Nutrients. 2019;11(3):521.
• Socała K, Doboszewska U, Szopa A, Serefko A, Włodarczyk M, Zielińska A, et al. The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders. Pharmacological Research. 2021;172:105840.
• Ersöz Alan B, Gülerman F. Otizm Spektrum Bozukluğunda Bağırsak Mikrobiyotasının Rolü. Turkish Journal of Psychiatry. 2019;30(3).
• Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe. 2010;16(4):444-53.
• Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC gastroenterology. 2011;11(1):1-13.
• Parracho HM, Bingham MO, Gibson GR, McCartney AL. Differences between the gut microflora of children with autistic spectrum disorders and that of healthy children. Journal of medical microbiology. 2005;54(10):987-91.
• Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism–comparisons to typical children and correlation with autism severity. BMC gastroenterology. 2011;11(1):22.
• Tomova A, Husarova V, Lakatosova S, Bakos J, Vlkova B, Babinska K, et al. Gastrointestinal microbiota in children with autism in Slovakia. Physiology & behavior. 2015;138:179-87.
• Williams BL, Hornig M, Parekh T, Lipkin WI. Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances. MBio. 2012;3(1):10.1128/mbio. 00261-11.
• De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, et al. Fecal microbiota and metabolome of children with autism and pervasive developmental disorder not otherwise specified. PloS one. 2013;8(10):e76993.
• Sandler RH, Finegold SM, Bolte ER, Buchanan CP, Maxwell AP, Väisänen M-L, et al. Short-term benefit from oral vancomycin treatment of regressive-onset autism. Journal of child neurology. 2000;15(7):429-35.
• Yitik Tonkaz G, Esin IS, Turan B, Uslu H, Dursun OB. Determinants of Leaky Gut and Gut Microbiota Differences in Children With Autism Spectrum Disorder and Their Siblings. Journal of Autism and Developmental Disorders. 2022:1-14.
• Dicksved J, Halfvarson J, Rosenquist M, Järnerot G, Tysk C, Apajalahti J, et al. Molecular analysis of the gut microbiota of identical twins with Crohn's disease. The ISME journal. 2008;2(7):716-27.
• Geier DA, Geier MR. A clinical and laboratory evaluation of methionine cycle-transsulfuration and androgen pathway markers in children with autistic disorders. Hormone Research in Paediatrics. 2006;66(4):182-8.
• Geier DA, Kern JK, Garver CR, Adams JB, Audhya T, Geier MR. A prospective study of transsulfuration biomarkers in autistic disorders. Neurochemical research. 2009;34:386-93.
• Nirmalkar K, Qureshi F, Kang DW, Hahn J, Adams JB, Krajmalnik-Brown R. Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy. Int J Mol Sci. 2022 Nov 3;23(21):13481. doi: 10.3390/ijms232113481.
• Xu M, Xu X, Li J, Li F. Association between gut microbiota and autism spectrum disorder: a systematic review and meta-analysis. Frontiers in psychiatry. 2019;10:473.
• Aktories K, Just I. Clostridial Rho-inhibiting protein toxins. Bacterial Virulence Factors and Rho GTPases. 2005:113-45.