Researchers have developed a urine-based screening tool that may help identify individuals who are most likely to be diagnosed with autism later in life, opening the door to assessment and support networks.
In a study of 99 children aged between two and 11 years – 52 diagnosed with autism spectrum disorder (ASD) and 47 who were developing “typically” – Arizona State University (ASU) researchers measured 17 microbially derived metabolites (MDMs) excreted in urine. These small, microbe-produced molecules are significantly more prevalent (up to 1,000 times higher than the control) in individuals with ASD, making them prime candidates for a clinical test.
Using these findings, the team developed what it calls the Microbially-Derived Metabolite (MDM) System – a scoring tool that classified ASD children in the study with 90% sensitivity and 100% specificity.
“Many studies have confirmed that a subset of children with autism spectrum disorder have unusually high urinary concentrations of microbially-derived metabolites (MDMs) such as p-cresol sulfate and indoxyl sulfate,” the researchers wrote. “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.”
In fact, more than 40 other studies have identified elevated microbial metabolite levels that the MDM System registered as ASD-linked.
The findings don’t imply that gut metabolites cause autism, nor that altering them would have any impact; the urine test is not intended as a stand-alone diagnostic tool, and, given the cohort, larger studies are needed.
What’s more, ASD – and neurodivergence (ND) in general – is not something that needs fixing or “curing”, which the scientists here emphasize. What is needed, though, is the development of diagnostic tools that examine biology, not just behavior. ASD, like attention-deficit/hyperactivity disorder (ADHD), is now understood to be predominantly genetic, with up to 90% heritability. Basically, it’s in the genome.
A Nature study published in April touched on the importance of early diagnosis. And as someone who spent more than 30 years without an ADHD diagnosis, I am acutely aware of how the “uncertainty” this paper touches on can show up. It makes early genetic- or biomarker-based tests so important.
This latest study adds to a growing body of evidence that the gut microbiome may contribute to some biological differences seen across ASD – and could eventually help identify subgroups of individuals who may benefit from more personalized support.
Metabolites from tyrosine, tryptophan and phenylalanine – all amino acids that play important roles in neurotransmitter pathways – were among those compounds implicated in the 17 identified by the researchers.
Andy DeLisle/ASU
“What we’ve discovered is that 80 to 90% of children with autism have extremely high levels of one or more microbially derived metabolites,” says Christina Flynn, first author and recent ASU PhD graduate. “Using this test will tell you which young children are at high risk for being diagnosed with autism, and guide treatment in those who have already been diagnosed to help them lead their best lives.”
ASD kids had an average of three gut metabolites at elevated levels, compared with the control cohort. In fact, children without a diagnosis had no remarkable metabolites in their urine at all.
“What’s really striking about the bacteria is that they make metabolites that are basically altered versions of serotonin and dopamine,” says Professor James Adams, corresponding author and a researcher with the Biodesign Center for Health Through Microbiomes, who also has an adult daughter with ASD.
“These are two key neurotransmitters that affect mood, cognition and memory,” he adds. “This could explain many of the symptoms and co-occurring symptoms in children with autism – their social communication, anxiety, depression and attention.”
It’s unclear how adjusting levels of MDMs could impact ASD symptoms, but the scientists emphasize that their findings are aimed at improving current diagnostic tools that go beyond traditional behavior-focused tests.
“We think reducing the levels of these metabolites may help these children lead healthier and happier lives, and we encourage children to be screened sooner to receive earlier interventions,” Adams adds.
And a key part of leading “healthier and happier lives” is broadening the scope of diagnostic tools from behavior to biology.
“We hope there is a reduction in stigma and shame associated with the condition,” says Flynn, who also has a child with ASD. “Sometimes diagnostic hesitancy happens because parents feel like they’re not good enough parents and they’re being judged. But that’s not the case because if we can detect it in urine, it’s a biology-based condition. Hopefully that will prevent any hesitancy on parents’ parts to seek treatment and seek it as early as possible.”
Illustration by Sophia Franz/ASU
The researchers also propose adding an ASD subtype – “ASD associated with microbially-derived metabolites”, or ASD-MDM – a phenotype seen in an estimated 90% of cases.
“For more than 15 years, I have been doing research on the gut microbiome and its potential contributions to human health, and autism spectrum disorder has been at the core of our research,” says co-author Professor Rosa Krajmalnik-Brown.
“I am excited about the MDM test, which includes important microbial metabolites, previously hypothesized to be linked with autism,” she adds. “This test can be a great way to assess this important microbial contribution.”
The urine test is now available in the US, with Analutos, a UK partner lab, also offering this diagnostic tool internationally.
“For many families, one of the biggest challenges is the waiting – the not knowing,” Flynn adds. “If this test shortens that gap, even by a little, that’s meaningful because earlier intervention can really help.”
The research was published in the journal Molecular Psychiatry.
Source: Arizona State University
Fact-checked by Mike McRae
