Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype
Mol Psychiatry 31, 5323–5333 (2026).
Christina K. Flynn, Kevin Carr, Paul Whiteley, Khemlal Nirmalkar, Andrew Bellinghiere, Juergen Hahn, Hongbin Liu, Halil Arici, Laura Hewitson, Morgan Devlin, Elena L. Pollard, Khyatiben V. Pathak, Krystine Garcia Mansfield, Anakaren Rosales Torres, Patrick Pirrotte, Daniel B. Kalb, Rebekah Keen, Victoria Kenyon, Alessio Fasano, Rosa Krajmalnik-Brown, James B. Adams & Sarah Kadzielski
Many studies have confirmed that a subset of children with autism spectrum disorder (ASD) have unusually high urinary concentrations of microbially-derived metabolites (MDMs) such as p-cresol sulfate and indoxyl sulfate. We hypothesized that these MDMs may affect neurodevelopment through the gut-brain axis and that a sub-phenotype characterized by gut dysbiosis may be present in most ASD individuals. This multi-site study involved measuring the concentrations of many MDMs in the urine of 52 children with ASD and 47 healthy, typically developing (TD) children, aged 2 to 11 years. The measurements were conducted first with semiquantitative Liquid Chromatography and Mass Spectrometry (LC-MS), followed by targeted quantitative LC-MS. The ASD group had significantly higher concentrations of many MDMs compared to the TD group. The MDMs included phenylalanine-derived, tryptophan-derived, and yeast-derived MDMs. Almost all children with ASD had one or more MDMs at concentrations above any TD child, and sometimes 100–1000× higher. The children with ASD had an average of 3 MDMs at levels above any TD child, compared to zero (by definition) for the TD children. Classification using one or more elevated MDM yielded a sensitivity of 90% and a specificity of 100%. This MDM SystemTM is a promising non-invasive method for diagnostic screening for ASD in children ages 2 to 11 years. These data also suggest approximately 90% of children with ASD have a distinct phenotype of ASD, which we propose naming ASD associated with Microbially-Derived Metabolites (ASD-MDM), defined by objective, quantitative laboratory measurements of these metabolites in urine.
