Metabolite-Based Biomarkers for Autism Spectrum Disorder: Current Research Progress

Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder. Its global prevalence has risen significantly and continuously in recent years, currently affecting approximately 1 in 36 individuals in the United States, making it a major worldwide public health concern. The etiology of ASD is complex, involving genetic, environmental, and interactive factors. Within this multifactorial framework, dysregulation of metabolic pathways is increasingly recognized as a pivotal driver in ASD pathogenesis. Although previous investigations have primarily focused on metabolite abnormalities within isolated pathways or specific biospecimens (e.g., blood, urine), the collective evidence remains fragmented, lacking a systematic and integrative characterization of metabolic disturbances in ASD. To address this gap, this review aims to systematically synthesize and evaluate metabolic biomarkers associated with ASD. We categorize these biomarkers according to their core pathobiological functions into five interrelated mechanistic domains for detailed discussion: neurotransmitter dysfunction, immune dysregulation, mitochondrial dysfunction, oxidative stress, and gut microbiota dysbiosis. By integrating the current evidence, we not only delineate characteristic metabolite alterations within each domain but also explore the potential cross-talk between these pathways. The identification of candidate biomarkers for early detection and to inform future strategic directions for the development of ASD interventions.