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

Shaohan Zhang, Kevin Liu, Leo Shi, Chuyao Yan, Alma Wang, Ashley Liu, Haiyi Guo, Alex Xie et al.

Nutrients, 2026

Abstract

Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: Although limited by a small sample…

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Evidence Hub reads this as a case series, done in people. Its evidence level is 5 of 5 (Very low · case / narrative / animal / in vitro / in silico). Case reports, narrative reviews, and animal, cell or computer-model studies give the weakest evidence for human health.

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