Psychobiotics in pediatric autism spectrum disorder: A systematic review of efficacy, mechanisms, and clinical translation

Figure 5 Mechanisms by which prebiotics influence the gut-brain axis in autism spectrum disorder. Prebiotics are non-digestible dietary substrates that selectively stimulate the growth and metabolic activity of beneficial gut microorganisms, thereby modulating host physiology through the gut-brain axis. Following ingestion, prebiotics such as galacto-oligosaccharides, fructo-oligosaccharides, and inulin are fermented by commensal bacteria, including Bifidobacterium and Lactobacillus species. This fermentation process increases the production of short-chain fatty acids, particularly acetate, propionate, and butyrate, which play critical roles in maintaining intestinal epithelial integrity, regulating immune responses, and influencing neuronal signaling pathways. In the gastrointestinal tract, prebiotic-induced microbial shifts can enhance mucosal barrier function, reduce intestinal permeability, and decrease gastrointestinal symptoms frequently observed in children with autism spectrum disorder (ASD). Systemically, microbial metabolites and immune mediators may enter the circulation and interact with the central nervous system through neural (vagus nerve), immune, and metabolic pathways. These mechanisms may contribute to modulating neuroinflammation, neurotransmitter synthesis (e.g., serotonin and γ-aminobutyric acid), and brain signaling processes associated with social behavior, cognition, and emotional regulation. Collectively, these interconnected pathways illustrate how prebiotic supplementation may influence both gastrointestinal health and neurobehavioral outcomes in ASD through microbiome-mediated modulation of the gut-brain axis. GI: Gastrointestinal; GOS: Galacto-oligosaccharides; PHGC: Partially hydrolysed guar gum; HPA: Hypothalamic-pituitary-adrenal axis; SCFAs: Short-chain fatty acids.