Elevated Microbially-Derived Metabolites in Autism: A Possible Diagnostic Screening Test for a Distinct ASD Phenotype

Area of Science:

• Neuroscience
• Metabolomics
• Pediatrics

Background:

• Autism spectrum disorder (ASD) is associated with elevated urinary microbially-derived metabolites (MDMs) in some children.
• These MDMs may impact neurodevelopment via the gut-brain axis.
• A gut dysbiosis sub-phenotype is hypothesized in most ASD individuals.

Purpose of the Study:

• To investigate urinary MDM concentrations in children with ASD compared to typically developing (TD) children.
• To explore the potential of MDMs as biomarkers for ASD diagnosis and sub-phenotyping.
• To identify a distinct ASD phenotype characterized by MDMs, termed ASD-MDM.

Main Methods:

• Multi-site study involving 52 children with ASD and 47 TD children (ages 2-11).
• Urine samples analyzed using untargeted and targeted Liquid Chromatography and Mass Spectrometry (LC-MS).
• Quantification of various MDMs, including phenylalanine-derived, tryptophan-derived, and yeast-derived metabolites.

Main Results:

• Children with ASD exhibited significantly higher concentrations of numerous MDMs compared to TD children.
• Nearly all ASD children had elevated MDMs, with some concentrations 100-1000x higher than TD controls.
• Classification based on elevated MDMs achieved 90% sensitivity and 100% specificity for ASD detection.

Conclusions:

• Elevated urinary MDMs are a significant finding in children with ASD, suggesting a gut-brain axis connection.
• The MDM System™ shows promise as a non-invasive diagnostic screening tool for ASD in children aged 2-11.
• Approximately 90% of ASD cases may represent a distinct phenotype, ASD-MDM, identifiable through urinary metabolite profiling.