The identification of metabolites from gut microbiota in autism spectrum disorder via network pharmacology.

Scientists used computer modeling to study how substances made by gut bacteria might affect autism. They found that certain bacterial products, including short-chain fatty acids and other compounds, may interact with specific genes and biological pathways linked to autism. The research suggests these gut bacteria products could play a role in autism development through the gut-brain connection, though this is based on computer analysis rather than testing in people.

This computational study used network pharmacology and molecular modeling to investigate how gut microbiota-derived metabolites may influence autism spectrum disorder (ASD). Researchers analyzed databases to identify 51 core targets linking ASD-related genes with gut metabolite targets. The analysis highlighted AKT1 and IL6 as key regulatory genes, with associations to PI3K/Akt and IL-17 signaling pathways. Eight metabolites were identified as potentially important, including short-chain fatty acids (acetate, butyrate, propionate) and indole derivatives.

Molecular docking analysis suggested strong binding between specific metabolites and target proteins. The study proposes a theoretical framework for understanding microbiota-gut-brain axis dysfunction in ASD through metabolite-mediated mechanisms.

While this computational analysis provides theoretical insights into gut-brain axis mechanisms in ASD, clinical translation requires experimental validation. The identified metabolites and pathways may inform future research directions for microbiota-based interventions, but direct therapeutic applications cannot be recommended based on this modeling study alone.

This is a computational study using database analysis and molecular modeling without experimental validation. No sample size reported and findings are theoretical. Clinical relevance requires validation through laboratory and human studies.

Autism spectrum disorder (ASD), a neurodevelopmental disorder affecting 1% of the global population, is increasingly associated with dysregulation of the microbiota-gut-brain axis. While genetic and environmental factors have been well-studied, the role of gut microbial metabolites in the pathogenesis of ASD remains underexplored. In this study, we integrated network pharmacology, molecular docking, and multi-database analysis to elucidate the molecular mechanisms by which gut microbiota-derived metabolites regulate ASD. Utilizing the gutMGene, GeneCards, and OMIM databases, we identified 51 core targets that intersect with ASD-related genes and gut metabolite targets.

Validation of four topological algorithms (Degree, EPC, MCC, MNC) identified AKT1 and IL6 as key pivotal genes, as revealed by protein-protein interaction (PPI) network analysis. Functional enrichment highlighted important associations with the PI3K/Akt and IL-17 signaling pathways. The Microbiome-Metabolite-Target-Signaling (MMTS) network linked eight key metabolites (e.g., short-chain fatty acids, indole derivatives) to AKT1/IL6 regulation. Drug similarity and toxicity assessments confirmed the safety of short-chain fatty acids (acetate, butyrate, propionate) and indole derivatives of the selected metabolites.

Molecular docking revealed a strong binding affinity between glycerylcholic acid (AKT1: - 10.2 kcal/mol) and 3-indolepropionic acid (IL6: - 4.9 kcal/mol), suggesting that they are closely related to ASD. This study provides a new research direction on the relationship between microbial metabolites and ASD and gives better help to future researchers.