A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Winter, 2017 | Number 1, Volume 31

“Leaky gut,” blood-brain barrier problems may play important role in autism

A “leaky gut” and a compromised blood-brain barrier may play key roles in autism spectrum disorders (ASD), according to new research. 

Increasingly, evidence is pointing to a gut-brain connection in autism. One possible scenario is that an overly permeable (“leaky”) gut allows neuroactive molecules to escape into the bloodstream, crossing an inadequate blood-brain barrier and entering the brain, where they cause neuroinflammation and affect behavior. 

To explore the gut-brain axis in autism, Maria Fiorentino and colleagues analyzed postmortem cerebral cortex and cerebellum tissues from 8 individuals with ASD, 10 individuals with schizophrenia, and 15 neurotypical controls. In addition, they analyzed intestinal epithelial tissue from 12 individuals with ASD and 9 controls. 

The researchers say that brain tissue samples from individuals with ASD exhibited altered expression of genes associated with blood-brain barrier integrity and function, as well as genes associated with inflammation. In addition, 75% of intestinal epithelial samples from individuals with ASD exhibited reduced expression of barrier-forming cellular components, and 66% showed a higher expression of molecules that increase intestinal permeability. The researchers say that “these findings seem to be specific for ASD,” although some anomalies were also seen in tissues from individuals with schizophrenia. 

Fiorentino comments, “This is the first time anyone has shown that an altered blood-brain barrier and impaired intestinal barrier might both play a role in neuroinflammation in people with ASD.” 

Fiorentino’s next project will involve analyzing the possible connection between gut microorganisms, intestinal permeability, and behavior. She says, “There is definitely something going on between the gut and the brain with ASD and other neurodevelopmental disorders, and of course, the microbiome has a big role to play. It has already been shown that ASD kids have an altered composition of gut microbial communities. If we can figure out what is required or missing, then maybe we can come up with a treatment that might be able to improve some of the behavioral issues and/or the gastrointestinal symptoms.”


Citations

“Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders,” Maria Fiorentino, Anna Sapone, Stefania Senger, Stephanie S. Camhi, Sarah M. Kadzielski, Timothy M. Buie, Deanna L. Kelly, Nicola Cascella, and Alessio Fasano, Molecular Autism, Vol. 7, No. 49, 2016. Address: Maria Fiorentino, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children, Boston, MA 02114, [email protected]

—and— 

“Study fi nds alterations in both blood-brain barrier and intestinal permeability in individuals with autism,” news release, Mass General News, January 18, 2017.