(PASADENA) – A breakthrough at Caltech suggests that behaviors associated with autism are influenced from gastrointestinal (GI) issues, and could be treated with probiotic therapy.
Using a mouse model of autism previously developed at Caltech, researchers injected the mice with the “good” human bacteria Bacteroides fragilis, which can treat a “leaky gut,” metabolites pouring out of the intestinal wall and into the bloodstream. Not only did the GI issue decrease, so did the autism symptoms in the mice. Now, neuroscientists and biologists at Caltech hypothesize that behavioral issues on the autism spectrum may be influenced by GI issues, and could be treated with probiotics.
“To be able to address both the GI issues and the behavioral issues, I think it’s like the Holy Grail,” said Sarkis Mazmanian, who was co-senior investigator with Caltech neuroscientist Paul Patterson.
The research was published online in the Dec. 5 issue of the journal “Cell,” and marks the first study demonstrating how changes in gut bacteria can influence autism-like behaviors in a mouse model, according to a news release. Leaky gut has also been measured in cases of Parkinson’s disease, multiple sclerosis and Alzheimer’s disease.
“The B. fragilis treatment alleviates GI problems in the mouse model and also improves some of the main behavioral symptoms,” senior research fellow and the study’s first author Elaine Hsiao said in a news release. “This suggests that GI problems could contribute to particular symptoms in neuropdevelopmental disorders.”
Mazmanian and Patterson began collaborating five years ago on the connection between GI problems (chronic constipation, chronic diarrhea, gastroesophageal reflux disease, etc.) and autism-like social and emotional behavior such as defects in social interaction and communication as well as repetitive behaviors. Caltech scientists managed to re-create all three disorders associated with autism in mice subjects by injecting pregnant mice with a viral mimic that triggers an infection-like immune response. The offspring exhibited autism-like behavior.
“In this study, we can provide a treatment after the offspring have been born that can help improve certain behaviors,” Patterson said. “I think that’s a powerful part of the story.”
Similarly, pregnant women who have a severe viral infection during pregnancy are of higher risk to give birth to a child with autism, according to a news release.
Mazmanian will be submitting a proposal to the FDA as early as January to begin human-subject testing. Like the mice, human subjects with autism symptoms and GI issues will be injected with Bacteroides fragilis. Bacteroides fragilis is only found in about 20 percent of humans, Mazmanian said.
Nine Caltech researchers worked on the study, which was funded by several grants and fellowships including one by Autism Speaks.
“This is really a landmark paper,” said Paul Wang, senior vice president of medical research for Autism Speaks. “It ties together a whole bunch of different threads of evidence we had and didn’t know if they fit together or not.”
Compared wth the brain, where autism-like behaviors have long been thought to originate, the stomach is a comparatively less complex area to study, Wang said. Though the study is still only in the animal research phase, it represents what could be a new approach to autism, Wang said.
“It’s certainly not the end of the road,” he said. “It just shows this is a very important issue that the autism community needs to continue exploring more deeply than it has and investing in this kind of research.”