A study conducted by USC’s Chan Division of Occupational Science and Occupational Therapy, in conjunction with other departments and UCLA researchers, published April 14 found that gut imbalances in children with autism are linked to behavioral symptoms and differences in emotional processing.

The study examined the gut microbiome of children, which produces metabolites — the result of body digestion — that influence brain activity. To analyze how this microbiome might correlate with autism symptoms, researchers collected stool samples, brain imaging data and behavioral assessments from 43 children with autism and 41 neurotypical children aged 8 to 17. 

Through this data, researchers found children with autism have lower levels of tryptophan-related metabolites than neurotypical children, which correlated with sensory sensitivity, gastrointestinal issues and increased severity of autism symptoms.

“We know that through evolution, the enteric nervous system, which is the neurons that go between our gut and our brain, is probably our first brain,” said lead researcher Lisa Aziz-Zadeh, an associate professor of occupational therapy, psychology and neuroscience. “Then the question is, ‘What are they sending information about? Who are they talking to in the gut?’”

Aziz-Zadeh said the research team was originally investigating potential brain differences in children with autism but pivoted to examining the gut after noticing differences in microbiomes. This led them to apply for a grant from the Department of Defense to expand the study and begin collecting stool samples. 

Aziz-Zadeh said the study’s findings could be used to further the understanding of the correlation between the gut and behaviors associated with autism severity. According to Aziz-Zadeh, one’s gut metabolite makeup can be affected by diet, probiotics, prebiotics, antibiotics or environmental factors.

“Knowing that there are 600 million neurons going from the gut to the brain, to ignore this completely would be ridiculous,” Aziz-Zadeh said. “It’s definitely part of the neural pathways.”

Ravi Bhatt, one of the study’s authors and a postdoctoral scholar at the Keck School of Medicine Neuroimaging and Informatics Institute, said expanding the research in a longitudinal study could help define the relationship between the gut and brain and children with autism.

“We’re not saying that these gut chemicals cause autism by any means, but our findings really support the idea that the gut microbiome may be playing a real role in shaping brain function,” Bhatt said. 

Sofronia Ringold, one of the study’s authors and a Ph.D. candidate in occupational sciences, said the study was unique because it emphasized the importance of collecting data from both children with autism and their families.

“In autism research, often there’s a critique that … we’re not collecting as much data from the perspective of the child,” Ringold said. “That was something that we wanted to incorporate, because they know about their experience the best.”

Ringold said the study was adapted to ensure the children who may have had sensory sensitivities were comfortable. Before researchers conducted MRI brain scans, participants were given practice MRI sessions a week in advance to prepare them for the real experience. Others were given earplugs or weighted blankets to help them stay still.

Ringold recalled one child who built a copy of the lab’s MRI machine out of Legos to prepare for the test.

“The MRI environment can be very uncomfortable for everyone — children, adults, autistic, non autistic — especially the sensory features of the MRI,” Ringold said. “It can be really loud. It’s also dark, [and] you have to stay as still as possible.”

Aziz-Zadeh said getting the children to give a stool sample was also challenging. To ease participants, researchers worked with occupational therapists and created videos explaining the study to children and their families. 

“My own daughter did it, and it was really, really hard,” Aziz-Zadeh said. “She did it as a [neuro]typical child in the control group … If you have a kid with autism, that’s even a lot harder.”

Conducting the study was made more difficult because by the coronavirus pandemic restrictions, which forced researchers to wear masks, plastic face shields and remain six feet apart. 

The research could be furthered with long-term studies that follow mothers and children with autism for the first few years of life or intervention studies that test the impact of diet and probiotics, Aziz-Zadeh noted.  

“I do think that people are more open to thinking about the gut microbiome,” Aziz-Zadeh said. “It has become more popular to think about the gut and how it can impact your body.”