Biology 103
Research Paper
Probiotic Therapy Alleviates Autism-Like Behaviors in Mice Autism spectrum disorder (ASD) is diagnosed when an individual exhibits characteristic behaviors that include repetitive actions, decreased social interactions, and impaired communication. Oddly enough, many individuals with ASD also suffer from gastrointestinal (GI) issues like abdominal cramps and constipation. Relating brain and GI 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 disorders. The microbiota in the GI have been previously 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 GI bacteria can influence autism-like behaviors in a mouse model. "Traditional research has studied autism as a genetic 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 physiology appears to have effects on what are currently presumed to be brain functions." The researchers used a mouse model of autism previously developed at Caltech to study this gut-microbiota-brain interaction. 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 replica that triggers an infection-like immune response in the mother and produces the core behavioral symptoms associated with autism in her babies. Mazmanian, Patterson, and their colleagues found that the "autistic" offspring of immune-activated pregnant mice also exhibited GI problems. In particular, the GI tracts of autistic-like mice were "leaky," which means that they allow material to pass through the intestinal wall and into the bloodstream. This characteristic has also been reported im some people with ABS. "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. To see whether these GI symptoms actually influenced the autism-like behaviors, the researchers treated the mice with Bacteroides fragilis, a bacterium that has been used as an experimental probiotic therapy in animal models of GI disorders. As a result, the leaky gut was fixed. Observations of the treated mice also showed that their behavior had changed. They were more likely to communicate with other mice, had reduced anxiety, and were less likely to engage in a repetitive digging behavior. "The B. fragilis treatment alleviates GI problems in the mouse model and also