Neurobiological Mechanisms Underlying the Therapeutic Effects of Physical Exercise in Autism Spectrum Disorder: A Narrative Review
DOI:
https://doi.org/10.12775/QS.2026.56.72377Keywords
Autism Spectrum Disorder×, Neuroinflammation, Physical Activity, Exercise, Microbiota, Gut-brain AxisAbstract
Background. Autism Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by impairments in social communication and the presence of restricted and repetitive behaviors. Increasing evidence suggests that structured physical exercise may serve as a supportive therapeutic approach. However, although exercise has been shown to improve both core symptoms and associated difficulties in ASD, the underlying biological mechanisms remain poorly understood.
Aim. This review aims to summarize current evidence on the neurobiological mechanisms that may underlie the beneficial effects of physical exercise in individuals with Autism Spectrum Disorder.
Material and methods. A narrative review of the literature was performed, focusing on studies exploring the interaction between physical exercise and neurobiological processes relevant to ASD. Studies were identified through databases such as PubMed and Scopus. Both clinical and preclinical studies were included to capture mechanistic insights related to brain function and structure.
Results. Physical exercise modulate ASD related mechanisms involving immune regulation, gut-brain communication, synaptic plasticity, and hormonal responses. Current evidence points to changes in microglial activation, cytokine profiles, and gut microbiota composition, although mechanistic data remain largely preclinical.
Conclusions. Structured physical exercise represents a promising complementary strategy in ASD, with potential benefits mediated through multiple neurobiological pathways. A better understanding of these mechanisms may support the development of targeted and individualized exercise based interventions tailored to the diverse needs of individuals with ASD.
References
Albantakis, L., Brandi, M. L., Brückl, T., Gebert, D., Auer, M. K., Kopczak, A., Stalla, G. K., Neumann, I. D., & Schilbach, L. (2021). Oxytocin and cortisol concentrations in adults with and without autism spectrum disorder in response to physical exercise. Comprehensive Psychoneuroendocrinology, 5. https://doi.org/10.1016/j.cpnec.2021.100027
Alzghoul, L., Abdelhamid, S. S., Yanis, A. H., Qwaider, Y. Z., Aldahabi, M., & Albdour, S. A. (2019). The association between levels of inflammatory markers in autistic children compared to their unaffected siblings and unrelated healthy controls. Turkish Journal of Medical Sciences, 49(4). https://doi.org/10.3906/sag-1812-167
Bozdagi, O., Sakurai, T., Papapetrou, D., Wang, X., Dickstein, D. L., Takahashi, N., Kajiwara, Y., Yang, M., Katz, A. M., Scattoni, M., Harris, M. J., Saxena, R., Silverman, J. L., Crawley, J. N., Zhou, Q., Hof, P. R., & Buxbaum, J. D. (2010). Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication. Molecular Autism, 1(1). https://doi.org/10.1186/2040-2392-1-15
Cassilhas, R. C., Tufik, S., & De Mello, M. T. (2016). Physical exercise, neuroplasticity, spatial learning and memory. In Cellular and Molecular Life Sciences (Vol. 73, Number 5). https://doi.org/10.1007/s00018-015-2102-0
Castaño, P. R. L., Suárez, D. P. M., González, E. R., Robledo-Castro, C., Hederich-Martínez, C., Cadena, H. P. G., Vargas, P. A. S., & Montenegro, L. C. G. (2024). Effects of Physical Exercise on Gross Motor Skills in Children with Autism Spectrum Disorder. Journal of Autism and Developmental Disorders, 54(8). https://doi.org/10.1007/s10803-023-06031-5
Chen, Y., Chen, X., Luo, Z., Kang, X., Ge, Y., Wan, R., Wang, Q., Han, Z., Li, F., Fan, Z., Xie, Y., Qi, B., Zhang, X., Yang, Z., Zhang, J. H., Liu, D., Xu, Y., Wu, D., & Chen, S. (2025). Exercise-Induced Reduction of IGF1R Sumoylation Attenuates Neuroinflammation in APP/PS1 Transgenic Mice. Journal of Advanced Research, 69. https://doi.org/10.1016/j.jare.2024.03.025
Fattorusso, A., Di Genova, L., Dell’isola, G. B., Mencaroni, E., & Esposito, S. (2019). Autism spectrum disorders and the gut microbiota. In Nutrients (Vol. 11, Number 3). https://doi.org/10.3390/nu11030521
Foxall, V., Leckey, J., Brandt, A., Jacques, S., & Johnson, S. (2025). The Effects and Characteristics of Exercise Interventions on Executive Functioning in Individuals with Autism Spectrum Disorder: A Scoping Review. In Review Journal of Autism and Developmental Disorders. https://doi.org/10.1007/s40489-025-00510-4
Haaf, R., Brandi, M. L., Albantakis, L., Lahnakoski, J. M., Henco, L., & Schilbach, L. (2024). Peripheral oxytocin levels are linked to hypothalamic gray matter volume in autistic adults: a cross-sectional secondary data analysis. Scientific Reports, 14(1). https://doi.org/10.1038/s41598-023-50770-5
Hughes, H. K., R.J.Moreno, & Ashwood, P. (2023). Innate immune dysfunction and neuroinflammation in autism spectrum disorder (ASD). In Brain, Behavior, and Immunity (Vol. 108). https://doi.org/10.1016/j.bbi.2022.12.001
Kamp-Becker, I. (2024). Autism spectrum disorder in ICD-11—a critical reflection of its possible impact on clinical practice and research. Molecular Psychiatry. https://doi.org/10.1038/s41380-023-02354-y
King, C., Rogers, L. G., Jansen, J., Sivayokan, B., Neyhard, J., Warnes, E., Hall, S. E., & Plakke, B. (2024). Adolescent treadmill exercise enhances hippocampal brain-derived neurotrophic factor (BDNF) expression and improves cognition in autism-modeled rats. Physiology and Behavior, 284. https://doi.org/10.1016/j.physbeh.2024.114638
Lan, W., Zhong, J., Li, Y., Shen, Y., Gong, J., Zou, Z., & Hou, X. (2026). Effects of exercise on behavior and hippocampal neuroinflammation in rat model of autism spectrum disorder. Brain, Behavior, & Immunity - Health, 53, 101208. https://doi.org/10.1016/J.BBIH.2026.101208
Li, Z., Yang, Q., Li, H., Ge, J., Yan, H., Li, J., Fu, Y., Yan, K., Li, S., Chen, J., Dou, W., Xu, J., Luo, J., Li, B., & Cao, W. (2025). Social memory engram formation impairment in neuroligin-3 R451C knock-in mice is caused by disrupted prefrontal NMDA receptor-dependent potentiation. Communications Biology, 8(1). https://doi.org/10.1038/s42003-025-08806-1
Liao, X., Yang, J., Wang, H., & Li, Y. (2020). Microglia mediated neuroinflammation in autism spectrum disorder. In Journal of Psychiatric Research (Vol. 130). https://doi.org/10.1016/j.jpsychires.2020.07.013
Liu, L., Tang, J., Liang, X., Li, Y., Zhu, P., Zhou, M., Qin, L., Deng, Y., Li, J., Wang, Y., Jiang, L., Huang, D., Zhou, Y., Wang, S., Xiao, Q., Luo, Y., & Tang, Y. (2024). Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress. Molecular Psychiatry, 29(7). https://doi.org/10.1038/s41380-024-02464-1
Marco, E. J., Hinkley, L. B. N., Hill, S. S., & Nagarajan, S. S. (2011). Sensory processing in autism: A review of neurophysiologic findings. Pediatric Research, 69(5 PART 2). https://doi.org/10.1203/PDR.0b013e3182130c54
Min, L., Ablitip, A., Wang, R., Luciana, T., Wei, M., & Ma, X. (2024). Effects of Exercise on Gut Microbiota of Adults: A Systematic Review and Meta-Analysis. Nutrients, 16(7). https://doi.org/10.3390/nu16071070
Mohammadkhani, R., Salehi, I., Safari, S., Ghahremani, R., Komaki, A., & Karimi, S. A. (2024). Continuous exercise training rescues hippocampal long-term potentiation in the VPA rat model of Autism: Uncovering sex-specific effects. Neuroscience, 559. https://doi.org/10.1016/j.neuroscience.2024.08.037
Pretorius, L., Coetzee, J. A., Santos, A. P. dos, & Smith, C. (2025). Modulating autism spectrum disorder pathophysiology using a trace amine-focused approach: targeting the gut. In Molecular Medicine (Vol. 31, Number 1). https://doi.org/10.1186/s10020-025-01232-3
Sgritta, M., Dooling, S. W., Buffington, S. A., Momin, E. N., Francis, M. B., Britton, R. A., & Costa-Mattioli, M. (2019). Mechanisms Underlying Microbial-Mediated Changes in Social Behavior in Mouse Models of Autism Spectrum Disorder. Neuron, 101(2). https://doi.org/10.1016/j.neuron.2018.11.018
Sharon, G., Cruz, N. J., Kang, D. W., Gandal, M. J., Wang, B., Kim, Y. M., Zink, E. M., Casey, C. P., Taylor, B. C., Lane, C. J., Bramer, L. M., Isern, N. G., Hoyt, D. W., Noecker, C., Sweredoski, M. J., Moradian, A., Borenstein, E., Jansson, J. K., Knight, R., … Mazmanian, S. K. (2019). Human Gut Microbiota from Autism Spectrum Disorder Promote Behavioral Symptoms in Mice. Cell, 177(6). https://doi.org/10.1016/j.cell.2019.05.004
Shen, Y., Zhong, J. G., Lan, W. T., Li, Y. H., Gong, J. H., Zhao, B. X., & Hou, X. H. (2023). Bibliometric study of neuroinflammation in autism spectrum disorder. In Frontiers in Psychiatry (Vol. 14). https://doi.org/10.3389/fpsyt.2023.1086068
Tang, G., Gudsnuk, K., Kuo, S. H., Cotrina, M. L., Rosoklija, G., Sosunov, A., Sonders, M. S., Kanter, E., Castagna, C., Yamamoto, A., Yue, Z., Arancio, O., Peterson, B. S., Champagne, F., Dwork, A. J., Goldman, J., & Sulzer, D. (2014). Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits. Neuron, 83(5). https://doi.org/10.1016/j.neuron.2014.07.040
Tu, G., Guo, Y., Xiao, R., Tang, L., Hu, M., & Liao, B. (2023). Effects of Exercise Training on the Phosphoproteomics of the Medial Prefrontal Cortex in Rats With Autism Spectrum Disorder Induced by Valproic Acid. Neurorehabilitation and Neural Repair, 37(2–3). https://doi.org/10.1177/15459683231152814
Usui, N., Kobayashi, H., & Shimada, S. (2023). Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder. In International Journal of Molecular Sciences (Vol. 24, Number 6). https://doi.org/10.3390/ijms24065487
Vilela, J., Rasga, C., Santos, J. X., Martiniano, H., Marques, A. R., Oliveira, G., & Vicente, A. M. (2024). Bridging Genetic Insights with Neuroimaging in Autism Spectrum Disorder—A Systematic Review. In International Journal of Molecular Sciences (Vol. 25, Number 9). https://doi.org/10.3390/ijms25094938
Wang, M., Zhang, X., Zhong, L., Zeng, L., Li, L., & Yao, P. (2025). Understanding autism: Causes, diagnosis, and advancing therapies. In Brain Research Bulletin (Vol. 227). https://doi.org/10.1016/j.brainresbull.2025.111411
Wegierska, A. E., Charitos, I. A., Topi, S., Potenza, M. A., Montagnani, M., & Santacroce, L. (2022). The Connection Between Physical Exercise and Gut Microbiota: Implications for Competitive Sports Athletes. In Sports Medicine. https://doi.org/10.1007/s40279-022-01696-x
Xue, Y., An, S., Qiu, W., Zhang, W., Fu, L., & Zhen, Z. (2022). Exercise Changes Gut Microbiota: A New Idea to Explain that Exercise Improves Autism. In International Journal of Sports Medicine (Vol. 44, Number 7). https://doi.org/10.1055/a-2018-2477
Zeidan, J., Fombonne, E., Scorah, J., Ibrahim, A., Durkin, M. S., Saxena, S., Yusuf, A., Shih, A., & Elsabbagh, M. (2022). Global prevalence of autism: A systemtic review update. In Autism Research (Vol. 15, Number 5). https://doi.org/10.1002/aur.2696
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Copyright (c) 2026 Justyna Kuś, Patrycja Białowąs, Natalia Zięba, Olgierd Czapiński, Anna Brodowska, Ewa Tomicka, Anna Knapik, Olga Stadnicka , Maciej Ciesielski, Mateusz Pysiewicz

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