An integrative multi-omics approach identifies microbiome alterations linked to pathological and behavioral features in autism spectrum disorder

Mar 10, 2026Cell reports. Medicine

Changes in the gut microbiome linked to physical and behavioral traits in autism

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Abstract

Microbial features could accurately distinguish ASD from TD children in a sample of 326 children with autism spectrum disorder and 169 typically developing controls.

An increase in Clostridioides difficile abundance is associated with greater ASD symptom severity and variations in brain structure.
Gut and brain differences are age dependent, diminishing as children with ASD grow older and converging toward patterns seen in typically developing children.
A mediation model indicates that specific gut microbes may influence brain structure and behavior through their metabolites.
The findings highlight the gut microbiota as a strong predictor of brain and behavioral characteristics in young children with ASD.

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This study employs a multi-omics approach to investigate the gut-brain axis in 326 children with autism spectrum disorder (ASD) and 169 typically developing (TD) controls, aged 0-10 years. By analyzing neuroimaging, gut microbiome, and plasma metabolome data, we find that microbial features could accurately distinguish ASD from TD children. A key finding is that gut microbial abundance, particularly an increase in Clostridioides difficile, serves as the strongest predictor of both ASD symptom severity and brain structural variations. Crucially, these gut and brain differences are age dependent, diminishing as children with ASD aged and converging toward TD patterns. A mediation model suggests a potential pathway where specific microbes influence brain structure and behavior via metabolites. The findings establish the gut microbiota as a robust predictor of brain and behavioral phenotypes in pediatric ASD, underscoring the necessity for early, age-stratified therapeutic strategies via modulating the composition of the gut microbiome.