Autism spectrum disorder and the gut-brain axis: diagnostic and therapeutic perspectives

Abstract

Autism Spectrum Disorder (ASD) is increasingly recognized as a neurodevelopmental condition influenced by complex interactions between genetic, immune, metabolic, and microbial factors. Growing evidence suggests that the bidirectional gut–brain axis—linking intestinal microbiota, immune activity, and neural pathways— plays a substantial role in behavioral and physiological regulation. A narrative synthesis was performed based on publications indexed in PubMed, Scopus, and Web of Science (2015–2025) focusing on clinical and translational studies that explored microbiota composition, immune and neurotransmitter modulation, and therapeutic interventions targeting the gut–brain axis in ASD. Inclusion criteria comprised peer-reviewed human or translational animal studies addressing microbial, inflammatory, and behavioral parameters. Based on the analysis of published studies, consistent patterns indicate that intestinal dysbiosis and epithelial barrier dysfunction contribute to systemic inflammation and altered neuroimmune signaling. Microbial metabolites modulate serotonergic, dopaminergic, and GABAergic pathways, influencing sensory processing, social interaction, and behavioral regulation. Integrated evaluation of clinical data shows small-to-moderate behavioral improvements and stable gastrointestinal benefits following microbiota-targeted approaches such as probiotics, psychobiotics, dietary modulation, and anti-inflammatory therapy. Behavioral domains most responsive include irritability, aggression, and emotional regulation, while global ASD severity shows limited change. These findings suggest that therapeutic modulation of the gut–brain axis acts primarily through restoration of microbial balance and neurochemical stability rather than direct modification of core autistic traits.