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

Microbial features could accurately distinguish ASD from typically developing children in a cohort of 326 ASD and 169 TD children aged 0–10 years.

• The study employed a multi-omics approach integrating neuroimaging, gut microbiome, and plasma metabolome data.
• Sample sizes were 326 children with ASD and 169 typically developing (TD) controls.
• Children ranged in age from 0 to 10 years.
• The multi-omics integration enabled discrimination between ASD and TD groups based on microbial features.

Clostridioides difficile abundance was identified as the strongest predictor of both ASD symptom severity and brain structural variations.

• Gut microbial abundance, particularly an increase in Clostridioides difficile, served as the strongest predictor.
• Predictions covered both behavioral (ASD symptom severity) and neuroimaging (brain structural) outcomes.
• This finding was identified within the multi-omics framework incorporating neuroimaging, microbiome, and metabolome data.

Gut and brain differences between ASD and TD children were age-dependent, diminishing as children with ASD aged and converging toward TD patterns.

• The differences in gut microbiome and brain structure were found to be age-dependent.
• As children with ASD aged, these differences diminished.
• ASD patterns converged toward typically developing patterns over time.
• This age-dependent pattern underscored the necessity for early, age-stratified therapeutic strategies.

A mediation model identified a potential pathway by which specific gut microbes influence brain structure and behavior via plasma metabolites.

• A mediation model was employed to assess the relationship between gut microbiota, metabolites, and brain/behavioral outcomes.
• The pathway runs from specific microbes through metabolites to brain structure and behavior.
• This finding integrated neuroimaging, gut microbiome, and plasma metabolome data.
• The mediation model supports a gut-brain axis mechanism in pediatric ASD.

The study establishes gut microbiota as a robust predictor of brain and behavioral phenotypes in pediatric ASD, supporting early, age-stratified microbiome-modulating interventions.

• Gut microbiota was described as 'a robust predictor of brain and behavioral phenotypes in pediatric ASD.'
• The findings underscore 'the necessity for early, age-stratified therapeutic strategies via modulating the composition of the gut microbiome.'
• The study design involved children aged 0–10 years to capture early developmental windows.
• The multi-omics approach integrated neuroimaging, gut microbiome, and plasma metabolome data across 495 total participants.