A new study from the University of Southern California suggests that gut imbalances in children with autism may cause a metabolite imbalance in the digestive system—ultimately hindering neurotransmitter production and influencing behavioral symptoms.
The research, published today in the journal Nature Communications, adds to a growing body of scientific evidence pointing to the involvement of the so-called “gut-brain axis” in autism. The discovery opens up the possibility for new treatment approaches. It is an example of how research conducted at USC and other universities drives innovation and leads to discoveries that improve lives.
“We have shown that gut metabolites affect the brain, and the brain, in turn, affects behavior. Essentially, the brain acts as an intermediary between gut health and autism-related behaviors,” said lead author Lisa Aziz-Zadeh, a professor at the Brain and Creativity Institute at USC Dornsife College of Letters, Arts, and Sciences. “Previous studies had already pointed to differences in gut microbiota and brain structures in people with autism, but our research connects these dots.”
The connection between the gut and the brain is not as unlikely as it may seem. From an evolutionary standpoint, the gut was probably the first “brain,” explained Aziz-Zadeh, who is also a professor in the Department of Psychology at USC Dornsife and in the Division of Occupational Science and Occupational Therapy at USC Mrs. T.H. Chan.
In fact, most of the neurons in the gut send signals to the brain; there are more neurons in the gut than in the spinal cord. About 90% of the neural signals between the gut and the brain travel from the gut to the brain, with only 10% traveling in the opposite direction.
This constant communication explains why we talk about “gut instinct” or “feeling it in the stomach.” Many emotions are processed by mechanisms linked to the gut, a concept known as interoception — the perception of the body’s internal sensations.
For the study, the researchers collected behavioral data, brain imaging, and stool samples from 43 children with autism and 41 neurotypical children, ages 8 to 17. From the stool samples, they analyzed the metabolites produced by gut bacteria responsible for breaking down food in the digestive system.
The researchers then correlated these metabolites with the brain differences observed in the children with autism and their behavioral characteristics. They focused on the “tryptophan pathway,” through which tryptophan — an amino acid found in many foods — is converted into various metabolites, including serotonin.
Serotonin is essential for emotional processing, social interaction, learning, and other brain functions. Since much of the body’s serotonin originates in the gut microbiota, changes in gut health can influence its production.
“We know that children with autism have brain differences — certain areas of the brain are either less or more active compared to children with typical development,” said Aziz-Zadeh. “We also know that they often have gastrointestinal problems, such as constipation, abdominal pain, and other digestive discomforts. Furthermore, autism is associated with various symptoms, including repetitive behaviors and social difficulties.”
Sofronia Ringold, a Ph.D. student at the Brain and Creativity Institute who participated in the study, said she was excited about the possibility of interventions that could act on the gut and influence neural activity and behavior “while also, hopefully, alleviating some of the more uncomfortable symptoms for these children.”
In addition to Aziz-Zadeh and Ringold, the other authors of the study are Aditya Jayashankar, Emily Kilroy, Ravi Bhatt, and Christiana Butera from USC; and Jonathan Jacobs, Skylar Tanartkit, Swapna Joshi, Mirella Dapretto, Jennifer Labus, and Emeran Mayer, all from UCLA.
The research was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD079432) and by a grant from the U.S. Department of Defense through the Idea Development Award (AR170062).
