Research squareNov 19, 2025

Higher Levels of Gut Bacteria Metabolites in Autism May Help Identify a Specific Type of ASD

Gut-Brain Axis Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jan 6, 2026

Abstract

Children with autism spectrum disorder (ASD) had significantly higher concentrations of harmful microbially-derived metabolites (MDMs) in their urine compared to typically developing children.

The ASD group exhibited elevated levels of various MDMs, including those derived from phenylalanine, tryptophan, and yeast.
Almost all children with ASD had at least one MDM at concentrations exceeding those of any typically developing child, sometimes by 100-1000 times.
On average, children with ASD had 3 MDMs at levels above any typically developing child, while typically developing children had zero.
Using the presence of elevated MDMs, classification achieved a sensitivity of 90% and a specificity of 100% for identifying ASD.
About 90% of children with ASD may have a distinct phenotype characterized by elevated MDMs, proposed as ASD associated with Microbially-Derived Metabolites (ASD-MDM).

Simplified

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 Systemis 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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Competing interests

Conflicts of Interest: JBA, CKF, RKB, JH, PW, and KC have patents and/or pending patents related to the diagnosis of ASD. JBA and RKB are co-founders of Autism Diagnostics LLC. JBA is the founder of Autism Diagnostics Lab Inc. PW and KC are co-owners of Analutos. JBA and RKB are co-founders of Gut-Brain-Axis Therapeutics Inc.

PubMed

Higher Levels of Gut Bacteria Metabolites in Autism May Help Identify a Specific Type of ASD

Abstract

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