Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype
14 affiliations
- 1Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, 85287, USA
- 2School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85287, USA
- 3Arizona State University
- 4ESPA Research, Sunderland, SR5 3RL, UK
- 5Department of Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA
- 6Rensselaer Polytechnic Institute
- 7The Johnson Center for Child Health and Development, Austin, TX, USA
- 8Early Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ, 85004, USA
- 9Cool Springs Family Medicine, Franklin, TN, 37067, USA
- 10Massachusetts General Hospital: Department of Gastroenterology, Boston, MA, 02114, USA
- 11Massachusetts General Hospital
- 12School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, AZ, 85281, USA
- 13Biodesign Center for Health Through Microbiomes, Arizona State University, Tempe, AZ, 85287, USA. [email protected]
- 14School for Engineering of Matter, Transport, and Energy, Arizona State University, Tempe, AZ, 85287, USA. [email protected]
Abstract
Many studies have confirmed that a subset of children with autism spectrum disorder (ASD) have unusually high urinary concentrations of harmful 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 untargeted 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 100-1000x 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 System™ 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 quantitative laboratory measurements of these metabolites in urine.
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BibTeX
@article{flynn2026elevated,
title = {{Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype}},
author = {Christina K. Flynn and Kevin Carr and Paul Whiteley and Khemlal Nirmalkar and Andrew Bellinghiere and Juergen Hahn and Hongbin Liu and Halil Arici and Laura C. Hewitson and Morgan Devlin and Elena L. Pollard and Khyatiben V. Pathak and Krystine Garcia and Anakaren Rosales Torres and Patrick Pirrotte and Daniel Kalb and Rebekah Keen and Victoria Kenyon and Alessio Fasano and Rosa Krajmalnik‐Brown and James B. Adams and Sarah Kadzielski},
journal = {Molecular Psychiatry},
year = {2026},
month = may,
doi = {10.1038/s41380-026-03620-5},
url = {https://doi.org/10.1038/s41380-026-03620-5},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype
AU - Christina K. Flynn
AU - Kevin Carr
AU - Paul Whiteley
AU - Khemlal Nirmalkar
AU - Andrew Bellinghiere
AU - Juergen Hahn
AU - Hongbin Liu
AU - Halil Arici
AU - Laura C. Hewitson
AU - Morgan Devlin
AU - Elena L. Pollard
AU - Khyatiben V. Pathak
AU - Krystine Garcia
AU - Anakaren Rosales Torres
AU - Patrick Pirrotte
AU - Daniel Kalb
AU - Rebekah Keen
AU - Victoria Kenyon
AU - Alessio Fasano
AU - Rosa Krajmalnik‐Brown
AU - James B. Adams
AU - Sarah Kadzielski
PY - 2026
DA - 2026/05/26
JO - Molecular Psychiatry
DO - 10.1038/s41380-026-03620-5
UR - https://doi.org/10.1038/s41380-026-03620-5
AB - Many studies have confirmed that a subset of children with autism spectrum disorder (ASD) have unusually high urinary concentrations of harmful 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 untargeted 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 100-1000x 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 System™ 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 quantitative laboratory measurements of these metabolites in urine.
SN - 1359-4184
SN - 1476-5578
ER -