Urine test could help identify children at risk for autism

A simple urine test could help identify children at risk for autism sooner than current assessments – opening the door to earlier diagnosis and treatment, and better long-term outcomes for children who have an autism spectrum disorder.

Arizona State University scientists and their colleagues have developed a new screening tool to test urine for 17 microbial metabolites – small molecules produced by microorganisms in the gut – in children ages 2 to 11 years old.

By measuring these compounds in urine, the team found that they could distinguish children with autism from typically developing children in their study groups with high accuracy.

And understanding the biological diversity within autism may help guide more targeted interventions, including approaches aimed at restoring a healthy gut microbiome.

Research, published today molecular psychiatryThe findings point to a consistent biological pattern in many children with autism – elevated levels of specific metabolites in the gut.

These include metabolites that come from tyrosine, tryptophan and phenylalanine – amino acids involved in key neurotransmitter pathways – as well as other compounds associated with yeast and fungal activity.

The new classification tool is called the “microbially-derived metabolite (MDM) system.” The system provides a score based on how many metabolites in the child’s urine exceed a normal reference range.

We found that 80 to 90% of children with autism have extremely high levels of one or more microbially derived metabolites. Using this test you will know which young children are at high risk of being diagnosed with autism, and those who have already been diagnosed will receive treatment guidance to help them live their best lives.”

Christina Flynn, first author of the study and recent ASU PhD graduate

Flynn attended the Ira A. Completed his doctoral studies in chemical engineering through the Fulton School of Engineering. Their research is part of work through the Biodesign Center for Health Through Microbiomes in the Biodesign Institute at ASU. She is now the Research Director of a newly launched CLIA-certified Autism Diagnostics Laboratory and serves as a Senior Research Scientist for Gut Brain Axis Therapeutics.

During trials, the urine test showed promising accuracy with 90% sensitivity and 100% specificity. This means it correctly identified 90% of children with autism, and did not misidentify any children without autism in the study.

Due to the study’s moderate sample size, additional confirmation of the test’s accuracy is ongoing to further validate the test.

Using advanced research techniques, the team measured the concentration of microbial-derived metabolites in 52 children with autism spectrum disorder and 47 typically developing children aged 2 to 11 years. Children from four geographic locations, including Arizona, Massachusetts, Tennessee, and Texas, participated in the study.

The differences were clear: Almost all children with autism had at least one metabolite level higher than the highest level seen in the control group, with some levels measuring 100 to 1,000 times higher. On average, children with autism spectrum disorders had about three elevated metabolites, while typically developing children had none.

“The really amazing thing about the bacteria is that they make metabolites that are basically altered versions of serotonin and dopamine,” said Presidential Professor James Adams, corresponding author of the study and a researcher at the Center for Biodesign for Health through Microbiomes.

“These are two key neurotransmitters that influence mood, cognition and memory. This may explain many of the symptoms and co-occurring symptoms in children with autism – their social communication, anxiety, depression and attention,” he said. Adams is also the father of an adult daughter with autism.

“We think reducing the levels of these metabolites can help these children live healthier and happier lives, and we encourage children to get screened early to receive earlier intervention,” said Adams of the School of Engineering of Matter, Transportation and Energy, part of the Ira A. Fulton School of Engineering.

early intervention

Current diagnostic tests rely on behavioral observations, and many families have to wait long periods of time for answers. Better developmental outcomes are associated with earlier identification and earlier intervention, whether medical, behavioral, or educational.

“We hope to reduce the stigma and shame associated with this condition,” said Flynn, who herself is the parent of a child with autism. “Sometimes diagnostic hesitation is because parents feel like they’re not good parents and they’re being judged. But that’s not the case because if we can detect it in the urine, it’s a biology-based condition. Hopefully that will stop any hesitation on the part of the parents to seek treatment and get it as quickly as possible.”

While the urine test is not a stand-alone diagnosis, researchers say it can help get children further in line for evaluation and specialized help.

A biological window into autism

In addition to screening, the findings also point to a possible biological pathway involved in many cases of autism. The metabolites measured in the test are largely produced by the gut microbiome. Some are known to affect the brain and are linked to neurotransmitters, including serotonin and dopamine, which play important roles in mood, cognition, and behavior.

This study is consistent with over 40 other studies that have found that several microbial metabolites measured in the MDM system are significantly higher in children with autism.

The team cautions that their research does not prove that these metabolites cause autism, even though some of them are strongly associated with symptoms associated with the disorder.

And based on their findings, the researchers have proposed a new subtype of autism called “ASD associated with microbial-derived metabolites,” or ASD-MDM. This phenotype comprises approximately 90% of cases of autism spectrum disorder. About 10% of the children with autism in the study did not have abnormal gut metabolites, however, most of those children had other major metabolic problems that were possibly linked to the genetic disorders.

“For more than 15 years, I have been researching the gut microbiome and its potential contribution to human health, and autism spectrum disorder has been at the core of our research,” said study co-author Professor Rosa Krajmalnik-Brown.

“I am excited about the MDM test, which includes important microbial metabolites previously known to be associated with autism. This test may be an excellent way to assess this important microbial contribution,” said Krajmalnik-Brown, director of the Biodesign Center for Health Through Microbiomes at ASU.

Some early research suggests that interventions such as microbiota-based therapy may affect metabolite levels and improve symptoms in some individuals. For example, the team’s first clinical trial of microbiota transplant therapy found that the treatment resulted in a significant reduction in a microbial metabolite, p-cresol sulfate, as well as significant improvements in gut symptoms and behavioral symptoms. However, the authors emphasize that more rigorous clinical trials are needed before such approaches can be widely recommended.

From laboratory to real-world use

The test, developed as part of Flynn’s doctoral research, is moving toward widespread availability. Analutos, a sister laboratory in the United Kingdom, is already offering urine testing internationally.

For younger children, testing can serve as a triage tool. For people already diagnosed, it can help physicians explore underlying biological factors and monitor how interventions affect the body over time.

cautious optimism

The researchers emphasize that more studies are needed to validate the findings in larger and more diverse populations, and to better understand how these metabolites relate to the development of autism.

Still, the potential impact is significant.

An estimated 1 in 31 children in the United States is affected by autism, and the lifetime cost of care averages $3.6 million per person.

Earlier detection and more personalized approaches can help improve quality of life – not just for individuals, but for entire families.

“For many families, one of the biggest challenges is the waiting — the not knowing,” Flynn said. “If this trial narrows that gap even a little bit, it’s worthwhile because earlier intervention can really help.”