Neurogastroenterological Dysregulation in Autism Spectrum Disorder: Barrier Function and Neural Communication

Autism Spectrum Disorder (ASD) is increasingly recognized not only as a neurodevelopmental condition but also as a multisystem disorder involving complex interactions among the gastrointestinal system, immune responses, the enteric nervous system, and the gut microbiota. In recent years, studies focusing on the microbiota-gut-brain axis have demonstrated that the gastrointestinal symptoms frequently observed in individuals with autism are closely associated with neurobehavioral manifestations. Increased intestinal permeability ("leaky gut"), gut microbiota dysbiosis, neuroinflammation, and immune activation are thought to play significant roles in the pathophysiology of autism. In particular, alterations in bacterial populations such as Clostridia, Desulfovibrio, and Sutterella may influence central nervous system functions through lipopolysaccharides, short-chain fatty acids, and neuroactive metabolites. Bidirectional communication mediated by the enteric nervous system and the vagus nerve is considered one of the principal mechanisms explaining the influence of the gut microbiota on behavioral processes, social interaction, and cognitive functions. Furthermore, microbiota-derived neuroactive compounds, including serotonin, Gamma-Aminobutyric Acid (GABA), and tryptophan metabolites, have been reported to serve as critical regulators of neurodevelopmental processes. This review aims to comprehensively evaluate the relationships among the gut microbiota, the enteric nervous system, and neuroimmune mechanisms from a neurogastroenterological perspective, thereby providing an integrated overview of current evidence regarding the etiopathogenesis of autism.