A quarterly publication of the Autism Research Institute
Spring 2025 | Number 2, Volume 39
A new study by U.S. researchers adds to evidence that the “gut-brain” axis plays a significant role in autism spectrum disorders (ASD).
Lisa Aziz-Zadeh and colleagues collected data on 43 children with ASD and 41 neurotypical children between eight and 17 years of age. The researchers evaluated the children’s behavior and analyzed stool samples obtained from them, looking specifically at metabolites in the tryptophan pathway. They also used functional magnetic resonance imaging (fMRI) to study the children’s brain function during tasks, focusing on brain regions involved in interoception (the awareness of internal sensations), emotions, and sensory processing.
Aziz-Zadeh comments, “We demonstrated that gut metabolites impact the brain, and the brain, in turn, affects behavior. Essentially, the brain acts as the intermediary between gut health and autism-related behaviors. Previous studies highlighted differences in gut microbiomes and brain structures in autism, but our research connects the dots.”
The researchers found that levels of several tryptophan-related fecal metabolites differed significantly between the two groups of children. In particular, children in the ASD group had lower levels of kynurenate (KA), a neuroprotective compound. The researchers note that a reduction in plasma levels of KA and a corresponding alteration of the ratio of KA to kynurenine (KYN)—a tryptophan metabolite that is neurotoxic— could “lead to neurotoxic effects, impact blood serotonin levels, and have profound behavioral and cognitive effects.”
Analyzing fMRI and behavioral data, the researchers found that “different fecal tryptophan metabolites are significantly correlated with task-based brain activity… and with ASD severity and symptomatology.” Aziz-Zadeh comments, “We demonstrated that gut metabolites impact the brain, and the brain, in turn, affects behavior. Essentially, the brain acts as the intermediary between gut health and autism-related behaviors. Previous studies highlighted differences in gut microbiomes and brain structures in autism, but our research connects the dots.”
The researchers note that they did not find any significant relationships between fecal KA levels and GI problems in the children with ASD, indicating that their findings may not be limited to children with GI issues.
“Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology,” Lisa Aziz-Zadeh, Sofronia M. Ringold, Aditya Jayashankar, Emily Kilroy, Christiana Butera, Jonathan P. Jacobs, Skylar Tanartkit, Swapna Mahurkar-Joshi, Ravi R. Bhatt, Mirella Dapretto, Jennifer S. Labus, and Emeran A. Mayer, Nature Communications, April 14, 2025 (free online). Address: Lisa Aziz-Zadeh, Mrs. T.H. Chan Division of Occupational Science and Occupational Therapy, University of Southern California, Los Angeles, CA 90089, [email protected].
—and—
“Gut imbalances in autism linked to brain and behavior changes,” Neuroscience News, April 14, 2025.
