Postbiotic Secondary Metabolites: Emerging Therapeutic Agents for Modulating the Gut-Brain Axis in Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with rising global prevalence, yet its definitive treatment remains elusive. The microbiota-gut-brain (MGB) axis has emerged as a critical pathway in ASD pathophysiology, with gut dysbiosis influencing neurodevelopment, immune regulation, and behavioral outcomes through microbial metabolites. Postbiotics, bioactive compounds derived from microorganisms including short-chain fatty acids (SCFAs), γ-aminobutyric acid (GABA), tryptophan derivatives, and exopolysaccharides, have garnered considerable attention as stable, safe, and targeted therapeutic agents. Recent preclinical studies demonstrate that postbiotic metabolites can modulate histone deacetylase activity, enhance neurotransmitter balance, reduce neuroinflammation, and promote neuroprotective gene expression. Clinical trials, including a multicenter randomized controlled trial of butyrate supplementation in ۱۲۸ children with ASD, are currently investigating the therapeutic efficacy of postbiotics on gastrointestinal and core behavioral symptoms. Concurrently, machine learning approaches are emerging as powerful tools to identify gut microbiome-derived metabolites as potential biomarkers for ASD, with Random Forest Classification models achieving a mean accuracy of ۸۵%, and to enable personalized postbiotic supplementation strategies tailored to individual gut profiles. This review synthesizes current evidence on postbiotic secondary metabolites in modulating the gut–brain axis in ASD, evaluates mechanistic and clinical findings, explores the transformative potential of artificial intelligence in postbiotic discovery and personalized intervention, and outlines a roadmap for integrating postbiotic science with AI-driven precision medicine.

کلیدواژه ها:

Autism Spectrum Disorder ، Postbiotics ، Secondary Metabolites ، Gut-Brain Axis ، Microbiome ، Precision Medicine