Autism spectrum¹ disorder² (ASD) is diagnosed when individuals exhibit characteristic behaviors that include repetitive actions, decreased social interactions, and impaired³ communication. Curiously⁴, many individuals with ASD also suffer from gastrointestinal（胃肠的） (GI) issues, such as abdominal⁶ cramps⁷ and constipation（便秘）. Using the co-occurrence of brain and gut⁸ problems in ASD as their guide, researchers at the California Institute Technology (Caltech) are investigating a potentially transformative new therapy for autism and other neurodevelopmental disorders⁹.

 

The gut microbiota -- the community of bacteria that populate the human GI tract¹⁰ -- previously¹¹ has been shown to influence social and emotional behavior, but the Caltech research, published online in the December 5 issue of the journal Cell, is the first to demonstrate that changes in these gut bacteria can influence autism-like behaviors in a mouse model.

 

"Traditional research has studied autism as a genetic¹² disorder and a disorder of the brain, but our work shows that gut bacteria may contribute to ASD-like symptoms in ways that were previously unappreciated," says Professor of Biology Sarkis K. Mazmanian. "Gut physiology¹³ appears to have effects on what are currently presumed to be brain functions."

 

To study this gut-microbiota-brain interaction, the researchers used a mouse model of autism previously developed at Caltech in the laboratory of Paul H. Patterson, the Anne P. and Benjamin F. Biaggini Professor of Biological Sciences. In humans, having a severe viral infection raises the risk that a pregnant woman will give birth to a child with autism. Patterson and his lab reproduced the effect in mice using a viral mimic¹⁴ that triggers an infection-like immune response in the mother and produces the core behavioral symptoms associated with autism in the offspring.

 

In the new Cell study, Mazmanian, Patterson, and their colleagues found that the "autistic" offspring of immune-activated pregnant mice also exhibited GI abnormalities. In particular, the GI tracts¹⁵ of autistic-like mice were "leaky," which means that they allow material to pass through the intestinal⁵ wall and into the bloodstream. This characteristic, known as intestinal permeability, has been reported in some autistic individuals. "To our knowledge, this is the first report of an animal model for autism with comorbid GI dysfunction," says Elaine Hsiao, a senior research fellow at Caltech and the first author on the study.

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