Development of a Metagenomics-Guided Personalized Synbiotic Protocol for Children with Autism Spectrum Disorder: An...

Gut microbiota dysregulation has been increasingly implicated in the pathophysiology of autism spectrum disorder (ASD), yet clinical responses to standardized probiotic interventions remain inconsistent, likely reflecting substantial inter-individual variability in baseline microbiome composition, host-microbe interactions, immune tone, and metabolic function. Here, we present a pilot implementation of a metagenomics-guided, personalized synbiotic intervention in children with ASD using the Systematic Microbiome Assessment and Reconstruction Therapy (SMART) framework.

Seven children (aged 5-12 years) underwent longitudinal fecal shotgun metagenomic profiling, and dietary habits, food sensitivities, and regional dietary background were recorded as contextual factors potentially influencing microbiome composition and response to intervention. Individualized synbiotic formulations were constructed based on microbial taxonomic composition and inferred functional capacity and iteratively refined over time. Gastrointestinal outcomes were assessed through caregiver-reported clinical observations, whereas behavioral changes were evaluated using standardized instruments.

Several participants demonstrated improvements in gastrointestinal symptoms and selected behavioral domains. Notably, in a subset of participants, improvements in gastrointestinal function preceded measurable behavioral changes.

Although limited by a small sample size and lack of a control group, these findings provide preliminary evidence supporting the feasibility of implementing a metagenomics-guided personalized synbiotic framework in ASD and generate hypotheses for future investigation. This work presents a preliminary conceptual framework for integrating microbial composition and inferred functional profiling into individualized intervention design and highlights the potential value of microbiome-informed stratification in future studies of treatment response. Larger controlled studies with objective outcome measures are warranted to further evaluate feasibility, reproducibility, and potential clinical utility.