University of Southern California: Newly published review covers current brain-gut-microbiome and autism literature

A new scoping review of nearly 200 publications covering the relationships between autism spectrum disorder and the brain–gut–microbiome system was published online today in Nutrients. The review synthesizes the growing body of research suggesting that gut microbiota — the trillions of microorganisms living within the human digestive system — may serve critical roles in modulating brain functions, social behaviors and autistic symptoms.

Two of the review’s co-first authors, Michelle Chernikova and Genesis Flores, were participants in USC’s Diversity, Inclusion, and Access JumpStart program, a structured summer research program for talented undergraduates considering pursuing a PhD degree, at the time of literature review and manuscript preparation.

Joining as co-first author is Emily Kilroy PhD ’18, Postdoc ’22, a postdoctoral scholar in the USC Chan Division of Occupational Science and Occupational Therapy. Jennifer Labus and Emeran Mayer, microbiologists at the University of California, Los Angeles, are co-authors. Senior author is Lisa Aziz-Zadeh, associate professor at the USC Chan Division jointly appointed to the USC Dornsife College of Letters, Arts and Sciences’ Brain and Creativity Institute.

The review synthesizes current understandings about the mechanisms by which gut microbiota, metabolic substances and the brain communicate to influence behaviors, including the different social–communication and restricted or repetitive patterns that characterize autism. Gastrointestinal symptoms such as abdominal pain, constipation and diarrhea have been reported in 46 to 84 percent of autistic people, giving recent rise to a hypothesis that gut dysregulation may be especially prevalent in autistic populations.

The paper was supported in part by Aziz-Zadeh’s four-year, $506,000 grant from the U.S. Department of Defense’s (DoD) Autism Research Program Idea Development Award.

“To date, most autism studies in humans either look at the brain and behavior, or at the gut microbiome and behavior,” Aziz-Zadeh said. “Our DoD study is one of the largest autism studies to look at all three factors together — brain, gut and behavior. The current paper in Nutrients lays down the theory behind this endeavor, reviewing everything from rodent studies on the topic, potential neurotransmitter pathways that may be involved and potential brain regions that may be modified by this interaction.”

Scientists have yet to determine the exact microbial composition associated with autism, and the authors recommend several future research directions. Those include the need for more standardized sampling, collection and analyses; research studying the prenatal gut microbiome in pregnant mothers; studies comparing the microbiomes of autistic and typically-developing populations; and longitudinal tracking of metabolic states and specific biomarkers through early childhood development.

As part of the USC Graduate School’s Diversity, Inclusion, and Access JumpStart program, Chernikova and Flores worked with Aziz-Zadeh for 10 weeks during USC’s summer session. The program joins USC researchers and laboratories with diverse undergraduates from outside USC, and provides academic and financial support, professional development and mentorship opportunities. It is designed to increase access and exposure to university research programs for underrepresented or nontraditional students, and is ultimately a pipeline to enhancing diversity within academia and the STEM workforce.

After completing the summer program, Chernikova and Flores stayed on as research assistants in Aziz-Zadeh’s lab, and both say they plan to continue working as research assistants through the spring of 2022.

Chernikova will earn her psychology and theater arts degrees from Loyola Marymount University in 2022. Flores earned a psychology degree from Cal Poly Pomona in 2020, and one day soon hopes to enter a clinical psychology PhD program to study the impact of early life stressors and adversity on mental health and behaviors.

“For this paper-writing experience specifically, I learned a lot about teamwork and collaboration,” Flores said. “Michelle [Chernikova] and I worked so closely on this paper, even though it was remote — we had Zoom calls until 1 a.m. brainstorming ideas, talking things out and really joining our thoughts together.”