<p>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 System<sup>TM</sup> 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&#xa0;objective, quantitative laboratory measurements of these metabolites in urine.</p>

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Elevated microbially-derived metabolites in autism: a possible diagnostic screening test for a distinct ASD phenotype

  • 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

摘要

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.