Developmental Trajectories of Gut Microbiota and Microbial Metabolites in Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) has been increasingly linked to gut microbial dysbiosis, yet the developmental trajectory of microbiota and microbial metabolites across childhood remains poorly understood. Here, we performed an integrated multi-omics analysis of gut bacterial taxa and faecal metabolites, including volatile organic compounds (VOCs), short-chain fatty acids (SCFAs), and amino acids (AAs), in 101 individuals with ASD and 105 age-matched neurotypical controls. The study was conducted in a well-powered, age-stratified pediatric cohort including toddlers, children, and adolescents. Our findings reveal early-life microbial dysbiosis in ASD, characterized by elevated alpha-diversity, altered community composition, and age-specific enrichment of taxa including Faecalibacterium, Bacteroides, Ruminococcus, Alistipes, and Roseburia. Network analyses demonstrated that toddlers exhibit smaller, sparser microbial interaction networks, while children and adolescents show increasingly complex and interconnected networks, compared with respective age-matched controls, suggesting a critical developmental window for microbiome-host interactions. Metabolomic profiling identified consistent ASD-associated alterations, including elevated aromatic and indole-derived VOCs (i.e., N-ethyl-benzenamine, 6-methyl-5-hepten-2-one, methyl isobutyl ketone), disrupted SCFA patterns, and reduced D-aspartate and D-alanine, indicating functional reprogramming of microbial fermentation and D-amino acid metabolism. Correlations between specific taxa and metabolites suggest that microbial community structure drives these metabolic outputs, with potential impacts on gut-brain signalling, immune modulation, and neurobehavioral phenotypes. These results support a model in which ASD involves early-life gut microbiota alterations that persist but evolve across development, highlighting potential microbial and metabolic biomarkers. Importantly, they underscore the translational potential of microbiome-targeted interventions during early childhood to modulate neurodevelopmental outcomes.