Summary: New research from USC shows that imbalances in the gut microbiome of children with autism are associated with altered production of metabolites that influence neurotransmitter systems such as serotonin. The study links these gut-derived metabolites to measurable differences in brain activity and to behavioral symptoms, suggesting that gut-brain communication plays a role in emotional processing, sensory sensitivity, and social behavior in autism.
The findings help explain why gastrointestinal issues are common in autistic children and point toward the potential for therapies that target gut health to reduce some autism-related symptoms.
Key Facts:
- Microbiome-Brain Link: Gut bacteria can shape brain function by altering tryptophan metabolism and the downstream production of serotonin and related compounds.
- Predominant Gut-to-Brain Signaling: A large majority of neural signals between the gut and the brain travel from the gut to the brain, underpinning how internal bodily states affect emotions and behavior.
- Autism Associations: Specific tryptophan-related metabolites in stool samples were lower in children with autism and correlated with both brain activity differences and measures of symptom severity.
Source: USC
Overview of the study
A new study by researchers at the University of Southern California examined how gut microbial metabolites relate to brain activity and behavior in children with autism spectrum disorder (ASD). Published in Nature Communications, the research integrates fecal metabolomics, task-based functional MRI (fMRI), and behavioral assessments to explore the so-called gut-brain axis in a pediatric autism sample.
The researchers collected stool samples, brain imaging data and behavioral measures from 43 children with autism and 41 neurotypical peers, ages 8–17. They focused on metabolites produced when gut bacteria break down tryptophan, an essential amino acid found in many foods. These metabolites influence serotonin synthesis and other biochemical pathways involved in mood, sensory processing and social behavior.
Analysis showed that levels of several tryptophan-related metabolites—including kynurenate—were significantly lower in children with ASD than in neurotypical children. These metabolite differences correlated with altered activity in brain regions previously implicated in autism, such as the insula and cingulate cortex. Importantly, brain activity in these regions mediated relationships between specific microbial metabolites and symptom measures like autism severity, disgust propensity, and sensory sensitivities.
‘Gut instinct’
The study reinforces the intuitive idea of “gut instinct.” Many internal sensations and emotions are processed through interoception—the brain’s interpretation of signals from within the body. From a biological perspective, the gastrointestinal system contains a dense network of neurons that continuously communicate with the brain. Researchers note that a majority of neural messaging between the gut and brain travels from the gut to the brain, which helps explain how changes in gut biochemistry can have powerful effects on mood and behavior.
Lead author Lisa Aziz-Zadeh, a professor at USC’s Brain and Creativity Institute, describes the findings as a step toward connecting previously observed differences in gut microbiomes and brain structure in autism. “We demonstrated that gut metabolites impact the brain, and the brain, in turn, affects behavior,” she said. Coauthor Sofronia Ringold, a doctoral student involved in the work, emphasized the translational promise: interventions that improve gut health may shift neural activity and alleviate both gastrointestinal discomfort and behavior symptoms for some children.
While the study is observational and does not establish direct causation, the multimodal approach—combining metabolomics, fMRI and behavioral data—provides converging evidence that gut-derived tryptophan metabolites relate to autism-relevant brain function and clinical features.
Research team and funding
Authors include Lisa Aziz-Zadeh, Sofronia Ringold, Aditya Jayashankar, Emily Kilroy, Ravi Bhatt, Christiana Butera (USC) and collaborators from UCLA. The study received support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD079432) and a Department of Defense Idea Development Award (AR170062).
About this microbiome and autism research news
Author: Leigh Hopper
Source: USC
Contact: Leigh Hopper – USC
Image: The image is credited to Neuroscience News
Original Research: Open access. “Relationships between brain activity, tryptophan-related gut metabolites, and autism symptomatology” by Lisa Aziz-Zadeh et al., Nature Communications.
Abstract (concise summary)
This cross-sectional, case-control study investigated fecal metabolomics, task-based fMRI responses, and behavioral measures in 43 children with ASD and 41 neurotypical children (ages 8–17). The study found lower fecal levels of specific tryptophan-related metabolites in ASD and identified associations between these metabolites, altered activity in insular and cingulate cortex regions, and ASD symptom severity. Activity in mid-insula and mid-cingulate regions mediated relationships between certain microbial metabolites and clinical measures, highlighting links between gut microbial tryptophan metabolism, interoceptive brain regions, and autism-related behaviors.