Otizm spektrum bozukluğunun mekanizmalarını anlamaya yönelik beyin-bağırsak-mikrobiyota ağı

ASD is a complex neurodevelopmental disorder associated with gastrointestinal issues and gut–brain axis disruptions. To examine ASD-related metabolic alterations and assess personalized interventions, a systems-level modeling approach was developed connecting host and microbial metabolism. Prefrontal cortex (PFC)-specific metabolic models were reconstructed to capture ASD-related alterations in a key executive region. Flux sampling revealed disrupted energy metabolism and elevated inflammatory and oxidative pathways. Sphingolipid metabolism was also affected, suggesting a promising direction for investigation. Colon models were also reconstructed to assess their capacity to handle neuroactive and microbially derived metabolites. At the microbiome level, personalized gut microbiota models were built using species-level metagenomic profiles and inferred diets from ASD, neurotypical, and microbiota transfer therapy treated children. ASD models showed reduced short-chain fatty acid secretion, redox imbalance, and impaired neurotransmitter production. Personalized whole-body models were created by adapting infant and adult models with individual microbiome, diet data, and age-specific physiology. Integration with PFC and microbial models enabled simulation of PFC-targeted, microbiota-modulated metabolic profiles. Among interventions, plant-based and fiber-rich diets most consistently reduced deviations from neurotypical PFC fluxes, while supplements like coenzyme Q10, iron, and calcium improved individual profiles. This systems approach reveals ASD-related metabolic disruptions and offers a framework for evaluating personalized nutritional and microbiome interventions. Interindividual variability emphasizes the need for personalized models that capture unique metabolic profiles for more precise and effective interventions.