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

Background: Many studies have confirmed that a subset of children with autism spectrum disorder (ASD) have unusually high urinary concentrations of harmful microbially-derived metabolites such as p-cresol. 

Method: This paper involved measuring the concentrations of many microbially-derived metabolites (MDMs) in the urine of 50 children with ASD and 47 healthy typically developing (TD) children, all aged 2 to 11 years, with untargeted and then targeted Liquid Chromatography and Mass Spectrometry (LC-MS). 

Results: The ASD group had significantly higher concentrations of 23 Microbial-Derived Metabolites (MDMs) compared to the TD group. The MDMs included phenylalanine-derived, tryptophan-derived, and yeast-derived MDMs.   A Microbial-Based Metabolite total score was developed for each participant, defined as the number of MDMs exceeding the highest value of the TD children. The mean MDM Total Score was 6.91 MDMs for the ASD group, ranging from zero to nine, compared to zero by definition for the TD group.  Classification using the MDM Total Score yielded a sensitivity of 90% and a specificity of 100%.

Conclusion: A large subset of children with ASD have significantly elevated concentrations of MDMs (above those of any TD child).  The MDM System is able to differentiate children with ASD vs TD with high sensitivity and specificity.   We propose a new ASD phenotype, one that is biochemically defined by one or more highly elevated MDMs, called the  ASD-Microbially-Derived Metabolites (ASD-MDM) Phenotype.