A research team at Arizona State University recently developed a urine-based screening tool that is expected to help early identify children who are more likely to be diagnosed with autism spectrum disorder (ASD) in the future, thus seizing a time window for follow-up evaluation and support services.
In one study of 99 children aged 2 to 11, 52 had been diagnosed with autism and 47 were typically developing. The researchers detected 17 types of metabolites (microbially derived metabolites, MDMs) produced by intestinal microorganisms in urine and found that the levels of these small molecules were significantly increased in children with autism, up to about 1,000 times higher than those in the control group. Therefore, they are considered to be strong candidates for clinical testing.
Based on these data, the team established a scoring tool called the "Microbially-Derived Metabolite System" (MDM System), which has a sensitivity of 90% and a specificity of 100% for identifying children with autism in this study sample. The study summary pointed out that a large number of studies in the past have confirmed that some autistic children have abnormally elevated levels of microbial metabolites such as p-p-cresol sulfate and indole sulfate in the urine. Based on this, the research team proposed that this type of MDMs is likely to affect neural development through the "gut-brain axis", causing many autistic individuals to present a subtype phenotype characterized by an imbalance of intestinal flora.
To date, more than 40 other studies have reported elevated microbial metabolites associated with ASD, and this new study further integrates relevant evidence into the MDM system. However, the researchers also emphasized that these results do not mean that intestinal metabolites cause autism, nor that symptoms can be improved by changing these metabolites. At present, this urine test is not a separate diagnostic tool, and its reliability and applicability still need to be verified in a larger sample.
The research team also reminds that autism, and neurodiversity (ND) more generally, is not a problem that needs to be "fixed" or "cured", but an inherent neurodevelopmental difference. The consensus in the scientific community is gradually shifting from "correcting behavior" to "understanding the biological basis." The goal of current research is to develop more diagnostic and screening tools based on biological indicators rather than single behavioral observations while respecting individual differences.
Existing research believes that neurodevelopmental conditions such as autism and attention deficit hyperactivity disorder (ADHD) mainly have a genetic basis. Their heritability can be as high as about 90%, and related characteristics are "written in genes." A study published in a journal of "Nature" in April this year once again emphasized the importance of early diagnosis, pointing out that long-term living in the uncertainty of "whether there are neurodevelopmental differences" will significantly affect an individual's quality of life and development trajectory.
This ASU study furthers the accumulation of evidence on the potential role of the gut microbiota in biological differences in autism, and suggests that in the future it may be used to identify certain subgroups that may be suitable for personalized support and intervention programs. Among the 17 compounds that have been focused on, they involve a variety of amino acid metabolites such as tyrosine, tryptophan, and phenylalanine. These amino acids play important roles in neurotransmitter pathways.
Studies indicate that approximately 80% to 90% of children with autism have "extremely high" levels of one or more metabolites of microbial origin in their urine. One of the first authors of the study, Christina Flynn, who just received her Ph.D. from ASU, said that using this test can screen out young children at high risk and provide additional information for already diagnosed children to guide individualized support so that they can live better lives.
In this study, children with autism had significantly elevated levels of an average of three intestinal metabolites, whereas no similarly significant abnormal metabolite patterns were found in children in the control group. James Adams, corresponding author of the paper and a researcher at the Center for Health Through the Microbiome at ASU's Biodesign Institute, pointed out that the metabolites produced by these bacteria are essentially "modified" analogs of serotonin and dopamine, which are key neurotransmitters that regulate functions such as mood, cognition, and memory. From this, the research team believes that this metabolite profile may, to a certain extent, explain the common symptoms of social communication difficulties, anxiety, depression, and attention problems in children with autism.
It is unclear whether adjusting the levels of these MDMs will have an impact on autism-related symptoms. The research team emphasizes that the focus at this stage is not to cure or reverse autism, but to improve existing diagnostic tools so that they no longer rely solely on behavioral scales and clinical observations. Adams said that if the levels of these metabolites can be reduced, it may help to improve the health and quality of life of the children involved, provided that the children can be screened at an earlier stage and receive earlier intervention and support.
The researchers also emphasized from a social perspective that shifting from a behavioral to a biological diagnostic perspective is expected to reduce the burden and stigma on parents. Flynn noted that some parents are on the fence about evaluations, in part because they fear their parenting abilities will be questioned, and a urine test that could reveal a biologically based condition might make them less hesitant and more willing to seek help sooner. She herself has an autistic child and feels this especially deeply.
In terms of diagnostic classification, the research team recommends adding a new autism subtype - "ASD associated with microbially-derived metabolites (ASD-MDM)". It is initially estimated that this phenotype may exist in about 90% of cases. Professor Rosa Krajmalnik-Brown, who participated in the study, said that over the past 15 years, she has continued to pay attention to the relationship between intestinal microbiota and human health, and autism spectrum disorder has always been one of the core of her research. This MDM test is expected to provide a simple and quantifiable new tool for assessing the contribution of intestinal microorganisms to autism.
Currently, this urine test has been launched in the United States and is provided to international users through the British collaborative laboratory Analutos to assist in children's autism risk screening and related research. For many families, the long wait and "the agony of not knowing the answer" are often the most difficult part. Researchers said that if this test can even slightly shorten the time gap from suspicion to evaluation, it would have practical significance, because the earlier intervention and support are obtained, the more beneficial it is to the long-term development of the child. The research results have been published in the academic journal "Molecular Psychiatry", and relevant popular science information is released by Arizona State University.