The neurobiological mechanisms underlying the effects of exercise interventions in autistic individuals

Autism spectrum disorder is a pervasive and heterogeneous neurodevelopmental condition characterized by social communication difficulties and rigid, repetitive behaviors. Owing to the complex pathogenesis of autism, effective drugs for treating its core features are lacking. Nonpharmacological approaches, including education, social-communication, behavioral and psychological methods, and exercise interventions, play important roles in supporting the needs of autistic individuals. The advantages of exercise intervention, such as its low cost, easy implementation, and high acceptance, have garnered increasing attention. Exercise interventions can effectively improve the core features and co-occurring conditions of autism, but the underlying neurobiological mechanisms are unclear. Abnormal changes in the gut microbiome, neuroinflammation, neurogenesis, and synaptic plasticity may individually or interactively be responsible for atypical brain structure and connectivity, leading to specific autistic experiences and characteristics. Interestingly, exercise can affect these biological processes and reshape brain network connections, which may explain how exercise alleviates core features and co-occurring conditions in autistic individuals. In this review, we describe the definition, diagnostic approach, epidemiology, and current support strategies for autism; highlight the benefits of exercise interventions; and call for individualized programs for different subtypes of autistic individuals. Finally, the possible neurobiological mechanisms by which exercise improves autistic features are comprehensively summarized to inform the development of optimal exercise interventions and specific targets to meet the needs of autistic individuals.