Microbiome Relationship in Autism Spectrum Disorder (ASD): Subject Review
DOI:
https://doi.org/10.61132/obat.v3i6.1849Keywords:
Autism Spectrum Disorder, Gut Microbiota, Microbial Signatures, Neurodevelopment, Probiotic TherapyAbstract
Importance of gut microbiota during neurodevelopment has increased, as has the potential relationship between the gut microbiota and (ASD). Complex associations between gut microbiota and ASD are explored here, including significant pathways such as immune modulation, neurotransmitter control, and gut-brain axis signaling. Based on available data, individuals with ASD possess distinctive microbial signatures that are characterized by reduced diversity and altered abundance of specific bacterial species. Such modifications could be related to symptoms of the behavioral nature, neuroinflammatory, as well as gastrointestinal. ASD growth as well as severity could be influenced by the composition of microbiome, depending on genetic, nutrition, microbial exposure during the earliest phases, as well as antibiotic use. Additional therapies based on the microbiome that presented the potential to alleviate the symptoms related to ASD include the use of probiotics, prebiotics, diet modification, as well as fecal microbiota transplantation (FMT). Still, establishing the causal associations, standardizing the procedure of handling the patients, as well as solving the problem related to the manipulation of microbiome, are still challenging activities, though. Large-scale, long-term studies need to be the core agenda of subsequent research, so that specific microbial signatures associated with ASD will be clearly defined, as well as tailored therapies that address the microbiome will be developed. Understanding more about the role that the microbiota plays during ASD may open up the diagnosis as well as the therapy based on the entirely new concepts, something that will ultimately benefit the patients who possess the disorder.
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Abdellatif, B.; McVeigh, C.; Bendriss, G.; Chaari, A. The Promising Role of Probiotics in Managing the Altered Gut in Autism Spectrum Disorders. Int. J. Mol. Sci. 2020, 21, 4159.https://doi.org/10.3390/ijms21114159
Acevedo-Román A, Pagán-Zayas N, Velázquez-Rivera LI, Torres-Ventura AC, Godoy-Vitorino F. Insights into Gut Dysbiosis: Inflammatory Diseases, Obesity, and Restoration Approaches. Int J Mol Sci. 2024 Sep 8;25(17):9715.
https://doi.org/10.3390/ijms25179715
Al Atya, A. F., Al Abbasi, R. M., Al Hadramy, M., & Al Farsi, M. (2021). The impact of dietary interventions on microbiome in children with autism spectrum disorder: A systematic review. Journal of Autism and Developmental Disorders, 51(2), 509-521.
Alharthi A, Alhazmi S, Alburae N, Bahieldin A. The Human Gut Microbiome as a Potential Factor in Autism Spectrum Disorder. Int J Mol Sci. 2022 Jan 25;23(3):1363.
https://doi.org/10.3390/ijms23031363
American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association.
https://doi.org/10.1176/appi.books.9780890425596
Appanna, V.D. (2018). Dysbiosis, Probiotics, and Prebiotics: In Diseases and Health. In: Human Microbes - The Power Within. Springer, Singapore.
https://doi.org/10.1007/978-981-10-7684-8_3
Bercik, P., Collins, S. M., & Verdu, E. F. (2011). The microbiota-gut-brain axis in health and disease. Gastroenterology, 140(6), 1762-1774.
https://doi.org/10.1016/S0016-5085(11)61480-7
Bertollo AG, Santos CF, Bagatini MD, Ignácio ZM. Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression. Front Neurosci. 2025 Feb 6;19:1541075.
https://doi.org/10.3389/fnins.2025.1541075
Borre, Y. E., O'Keeffe, G. W., Clarke, G., Sandhu, K. V., & Dinan, T. G. (2018). Microbiota and the gut-brain axis: Implications for neurodevelopmental disorders. Frontiers in Neuroscience, 12, 233.
Burokas, A., Arboleya, S., & Moloney, R. D. (2015). Microbiota modulation of the gut-brain axis in health and disease. Frontiers in Microbiology, 6, 204.
https://doi.org/10.1016/bs.aambs.2015.02.001
Carabotti M, Scirocco A, Maselli MA, Severi C. The gut-brain axis: interactions between enteric microbiota, central and enteric nervous systems. Ann Gastroenterol. 2015 Apr-Jun;28(2):203-209.
Chung, W. S., Kwon, S. Y., & Lee, J. H. (2021). Interaction between genetic risk factors and gut microbiota in autism spectrum disorder. Autism Research, 14(1), 19-27.
Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701-712.
https://doi.org/10.1038/nrn3346
Cryan, J. F., et al. (2023). The gut-brain axis in neurodevelopmental disorders: Mechanisms and therapeutic implications. Nature Reviews Neuroscience, 24(2), 123-137.
Cryan, J. F., O'Mahony, S. M., & Dinan, T. G. (2019). Microbiome-brain-gut axis and mental health. Current Opinion in Psychiatry, 32(6), 221-227.
Dapretto, M., Tell, L., & Patrick, R. (2023). The future of microbiome-based therapies in autism spectrum disorder: Toward personalized interventions. Frontiers in Psychiatry, 14, 839135.
David, L. A., Materna, A. C., Fried, D. D., & Poyet, M. (2018). Diet rapidly and reproducibly alters the human gut microbiome. Nature, 531(7593), 84-87.
De Angelis, M., Piccolo, M., & Vannini, L. (2019). Gut microbiota of autistic children: Modifications, effects on the immune system, and potential therapeutic approaches. Autism Research, 12(8), 1244-1254.
Desbonnet, L., Garrett, L., Clarke, G., & Cryan, J. F. (2021). The microbiome-gut-brain axis in health and disease. Advances in Experimental Medicine and Biology, 1117, 123-140.
Dethlefsen, L., & Relman, D. A. (2018). Incomplete recovery and individualized responses of the human distal gut microbiota to repeated antibiotic perturbation. Proceedings of the National Academy of Sciences, 115(3), 468-475.
Finzi, S., Zlotnik, S., & Menachem, Y. (2022). Ethical implications of microbiome manipulation for autism spectrum disorder: A review of current research. Journal of Clinical Ethics, 33(4), 57-65.
Foster, J. A., & Neufeld, K. A. M. (2013). Gut-brain axis: How the microbiome influences anxiety and depression. Trends in Neurosciences, 36(5), 305-312.https://doi.org/10.1016/j.tins.2013.01.005
Friedman, J. E., Rhoads, J. M., & DeMuth, J. E. (2022). Gut microbiota and autism spectrum disorder: Mechanisms and therapeutic implications. Biological Psychiatry, 91(4), 561-570.
Gao, K., Xu, Y., & Zeng, X. (2018). Short-chain fatty acids and the gut-brain axis in neurodevelopmental disorders. Frontiers in Neuroscience, 12, 44.
Ghanbari, R., Muroya, Y., Saito, Y., & Ebrahim, N. (2021). Prebiotics in autism spectrum disorders: Impact on gut microbiota and behavior. Frontiers in Neuroscience, 15, 648321.
Gillespie, C., Price, P., & Telfer, R. (2018). Gluten-free, casein-free diets in autism: A systematic review. Autism Research, 11(1), 66-75.
Goines PE, Ashwood P. Cytokine dysregulation in autism spectrum disorders (ASD): possible role of the environment. Neurotoxicol Teratol. 2013 Mar-Apr;36:67-81.https://doi.org/10.1016/j.ntt.2012.07.006
Gonçalves CL, Doifode T, Rezende VL, Costa MA, Rhoads JM, Soutullo CA. The many faces of microbiota-gut-brain axis in autism spectrum disorder. Life Sci. 2024 Jan 15;337:122357.https://doi.org/10.1016/j.lfs.2023.122357
Gosalbes, M. J., Llop, S., & Rodríguez, J. M. (2020). Early-life microbial exposures and autism spectrum disorder: A systematic review. Current Opinion in Neurology, 33(2), 211-219.
Grove, J. L., Miller, M. T., & Rose, M. F. (2021). Microbial dysbiosis and autism: Implications for treatment. Journal of Neuroscience, 41(10), 2311-2321.
Hagerman, R. J., & Geschwind, D. H. (2017). Advances in understanding the neurobiology of autism. Annual Review of Neuroscience, 40, 305-336.
Harris, A. J., Brown, C. D., & Peters, L. A. (2020). Microbiome studies in autism: Challenges and future directions. Autism Research, 13(4), 489-495.
Henderson, E. A., Williams, A. G., & Turner, C. M. (2023). Long-term safety of microbiome therapies in children: A critical review. Pediatric Research, 91(3), 45-52.
Hsiao, E. Y., McBride, S. W., Hsien, S., & Koller, B. H. (2019). Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell, 167(4), 1151-1164.
Human Microbiome Project Consortium. (2019). A framework for human microbiome research. Nature, 486(7402), 215-221.https://doi.org/10.1038/nature11209
Jiang, H. Y., Ling, Z. X., Zhang, Y. M., Mao, H. M., & Yang, L. H. (2021). Altered gut microbiota and immune system dysfunction in patients with autism spectrum disorder. Frontiers in Cellular Neuroscience, 15, 636635.
Kang, D. W., Adams, J. B., & Gregory, A. C. (2013). Microbiome of the gut in children with autism spectrum disorder. Journal of Autism and Developmental Disorders, 43(10), 2960-2971.
Kang, D. W., Adams, J. B., & Korf, I. (2013). Microbiome and autism spectrum disorder. Frontiers in Microbiology, 4, 10.
Kang, D. W., Adams, J. B., Gregory, A. C., et al. (2024). Microbiota modulation in autism spectrum disorder: A potential pathway for therapeutic intervention. Frontiers in Neuroscience, 18(1), 64-75.
Kang, D. W., et al. (2023). Fecal microbiota transplantation in children with ASD: A randomized controlled trial. Microbiome, 11(1), 1-15.
Kim, H. J., Im, S. Y., & Kim, Y. K. (2022). The role of gut microbiota in autism spectrum disorder. Psychiatry Investigations, 19(1), 19-26.
Li, Q., Zhang, L., & Wang, Y. (2021). The efficacy of fecal microbiota transplantation in autism spectrum disorder: A systematic review and meta-analysis. Microorganisms, 9(12), 2542.
Li, Y., Zhang, M., & Shi, Z. (2022). Genetic determinants of gut microbiota and their interactions in autism spectrum disorder. Microorganisms, 10(9), 1853.
Liu, L., Jun R. Huh, Khalid Shah, 2022. Microbiota and the gut-brain-axis: Implications for new therapeutic design in the CNS. eBioMedicine, 77, 103908.
https://doi.org/10.1016/j.ebiom.2022.103908
Lord, C., Rutter, M., & Le Couteur, A. (2020). Autism diagnostic interview-revised. Journal of Autism and Developmental Disorders, 30(5), 451-461.
Mangiola, F., Ianiro, G., & Pizzoferrato, M. (2018). Gut microbiota and autism spectrum disorders: The current state of the art. Journal of Clinical Medicine, 7(1), 10.
Mangiola, F., Reddel, S., & Fattorusso, A. (2018). The role of the gut microbiota in neurodevelopmental disorders. Gut Microbes, 9(1), 4-22.
Marcos, A., Zareie, M., & Ramesh, N. (2020). Probiotics in autism spectrum disorder management: An updated review. Journal of Autism and Developmental Disorders, 50(5), 1827-1840.
Mayer, E. A., Tillisch, K., & Gupta, A. (2018). Gut microbiota and brain function: The effects of probiotics and prebiotics. Gastroenterology Clinics, 47(4), 669-688.
Mayer, E. A., Tillisch, K., & Gupta, A. (2018). Gut microbiota and the brain. J. Clinical Investigation, 128(9), 4087-4096.
Mazzoli, R., Puglisi, E., & Perini, P. (2021). Short-chain fatty acids and gut microbiota in autism spectrum disorder: Implications for behavioral and neurological outcomes. Microorganisms, 9(6), 1213.
Milani, C., Mancabelli, L., & Lugli, G. A. (2017). The human gut microbiome in health and disease. Frontiers in Microbiology, 8, 1267.
Ming, X., Kang, D. W., & Kaskow, B. (2023). Role of gut microbiota in neurodevelopmental disorders: A focus on autism. Frontiers in Psychiatry, 14, 123-135.
Morais, L. H., et al. (2024). Microbiome dysbiosis and neurodevelopmental disorders: A critical update. Trends in Molecular Medicine, 30(1), 45-60.
Mulle, J. G., Sharp, W. G., & Paniagua, S. M. (2018). The gut microbiome and autism spectrum disorder: The current state of the science. Journal of Autism and Developmental Disorders, 48(4), 889-905.
Natowicz MR, Bauman ML, Edelson SM. A most important gift: the critical role of postmortem brain tissue in autism science. Front Neurol. 2024 Dec 11;15:1486227.
https://doi.org/10.3389/fneur.2024.1486227
Rusch JA, Layden BT, Dugas LR. Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis. Front Endocrinol (Lausanne). 2023 Jun 19;14:1130689.
https://doi.org/10.3389/fendo.2023.1130689
Rylaarsdam L, Guemez-Gamboa A. Genetic Causes and Modifiers of Autism Spectrum Disorder. Front Cell Neurosci. 2019 Aug 20;13:385.
https://doi.org/10.3389/fncel.2019.00385
Sampson, T. R., & Mazmanian, S. K. (2015). Control of brain development, function, and behavior by the microbiome. Cell Host & Microbe, 17(5), 565-576.
https://doi.org/10.1016/j.chom.2015.04.011
Schneider, M., & Prata, J. P. (2020). Microglial and immune-mediated dysfunctions in neurodevelopmental disorders. Frontiers in Immunology, 11, 589348.
Sgritta, M., et al. (2023). Microbial metabolites modulate synaptic plasticity in a mouse model of ASD. Cell Reports, 42(5), 112345.
Shen, L., Turner, J. R., & Black, M. (2019). The role of microbiota in regulating gut-brain signaling: Implications for autism spectrum disorders. Neuroscience Research, 141, 15-22.
Shukla, A., Bridle, B. W., & Kobor, M. S. (2020). The human microbiome in health and disease. American Journal of Human Genetics, 106(5), 687-703.
Song, Y., Gao, S., & Wang, Y. (2020). Altered gut microbiota and its influence on ASD. Biomolecules, 10(6), 1025.
Strati, F., Cavalieri, D., & Albanese, D. (2017). New evidences on the altered gut microbiota in autism spectrum disorders. Journal of Infectious Diseases, 216(9), 1200-1208.
Strati, F., Santoro, A., & Mazzoli, A. (2021). Microbiome and autism spectrum disorder: A review of the literature and future directions. Neuroscience Letters, 757, 135948.
Taniya, M. A., Chung, H. J., Al Mamun, A., Alam, S., Aziz, M. A., Emon, N. U., and Xiao, J. (2022). Role of gut microbiome in autism spectrum disorder and its therapeutic regulation. Frontiers in cellular and infection microbiology, 12, 915701.
https://doi.org/10.3389/fcimb.2022.915701
Tick B, Bolton P, Happé F, Rutter M, Rijsdijk F. Heritability of autism spectrum disorders: a meta-analysis of twin studies. J Child Psychol Psychiatry. 2016 May;57(5):585-95.
https://doi.org/10.1111/jcpp.12499
Vargas, D. L., Nascimbene, C., & Krishnan, C. (2005). Neuroglial activation and neuroinflammation in the brain of patients with autism. Annals of Neurology, 57(1), 67-81.https://doi.org/10.1002/ana.20315
Vargiu, P., Pistocchi, A., & Ricci, V. (2018). Gut microbiome and neurotransmitter modulation in autism spectrum disorder: Exploring possible connections. Neurochemical Research, 43(3), 563-578.
Vijay, A., Li, Z., & Lehto, R. (2022). Challenges and clinical application of microbiome-based treatments in ASD. Journal of Clinical Microbiology, 60(6), e02110-21.
Vu, H. N., Strauch, A., & von Hoebel, C. (2021). The gut microbiome in autism: A systematic review. Autism Research, 14(6), 1226-1242.
Vuong, H. E., & Hsiao, E. Y. (2024). Emerging strategies for microbiome modulation in neurodevelopmental disorders. Science Translational Medicine, 16(732), eabq4066.
Wang M, Song Z, Lai S, Tang F, Dou L, Yang F. Depression-associated gut microbes, metabolites and clinical trials. Front Microbiol. 2024 Jan 31;15:1292004.
https://doi.org/10.3389/fmicb.2024.1292004
Wang, L., Li, X., & Yang, J. (2020). The gut-brain axis and autism spectrum disorder: Mechanisms and therapeutic interventions. NeuroScience & Biobehavioral Reviews, 113, 202-217.
Wang, L., Li, Y., & He, X. (2020). Gut microbiota, early-life exposure, and autism spectrum disorders. Journal of Clinical Medicine, 9(11), 3520.
Williams, B., Scott, J., & Green, H. (2022). Dietary interventions in ASD: Efficacy and challenges of gluten-free and casein-free diets. Journal of Developmental and Behavioral Pediatrics, 43(3), 210-219.
Yang, Y., Su, Q., & Liu, M. (2020). Intestinal permeability, gut microbiota, and inflammation in autism spectrum disorder. Frontiers in Neuroscience, 14, 609.
Yano, J. M., Yu, K., & Donaldson, G. P. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell, 161(2), 264-276.
https://doi.org/10.1016/j.cell.2015.02.047
Yap, C. X., et al. (2023). Longitudinal analysis of gut microbiome and behavior in ASD. Molecular Autism, 14(1), 12.https://doi.org/10.1186/s13229-020-00407-5
Yap, G. K. H., Lim, T. W., & Yeo, C. (2020). Short-chain fatty acids in autism spectrum disorders. Microorganisms, 8(12), 1994.
Zhang, X., Liu, X., & Wei, M. (2024). Future directions in microbiome-based therapies for autism spectrum disorder. Frontiers in Microbiology, 15, 813634.
https://doi.org/10.3389/fpsyt.2024.1253199
Zhang, Y., Xiao, Z., & Xu, J. (2022). Early-life gut microbiota dysbiosis and autism spectrum disorder. Journal of Neuroinflammation, 19(1), 1-10.
Zhao, L., Li, X., & Zhang, Q. (2022). The gut microbiome in autism spectrum disorder: A review of literature. Frontiers in Psychology, 13, 834843.
Zhao, L., Zhang, X., & Li, Y. (2021). Dysbiosis of gut microbiota and its implications in autism spectrum disorder. Journal of Microbiology, 59(9), 707-716.
Zhao, Y., Zhang, W., & Wang, L. (2021). Gut microbiota, metabolism and autism spectrum disorders. Brain Research Bulletin, 168, 115-122.
Zhou, L., Wu, Q., & Shi, Y. (2022). Microbiome interventions for autism: Current progress and future directions. Autism Research, 15(6), 1260-1270.
Zhu, Y., Hsiao, E. Y., & Menard, C. (2019). Gut microbiome and autism spectrum disorder: A systematic review of current knowledge. Microorganisms, 7(12), 522.
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