The study, published in Cell,reported that the 'autistic' offspring of immune-activated pregnant mice also exhibited gastrointestinal (GI) abnormalities that have previously been associated with ASD in humans.
The study the first to demonstrate that changes in these gut bacteria can influence autism-like behaviours in a mouse model.
In particular, the team found that GI tracts of autistic-like mice were 'leaky' and allowed material to pass through the intestinal wall and into the bloodstream - a characteristic that has been reported in some autistic individuals.
The team behind the study also revealed that mice given Bacteroides fragilis - a bacterium that has been used as an experimental probiotic therapy in animal models of GI disorders - corrected the leaky gut and showed altered behaviours that is associated with reduced ASD symptoms, said the team.
In particular, mice fed the probiotic were more likely to communicate with other mice, had reduced anxiety, and were less likely to engage in a repetitive digging behaviour, the study found.
"To our knowledge, this is the first report of an animal model for autism with comorbid GI dysfunction," said first author Elaine Hsiao of California Institute Technology (Caltech).
"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," added Professor Sarkis K. Mazmanian. "Gut physiology appears to have effects on what are currently presumed to be brain functions."
"I think our results may someday transform the way people view possible causes and potential treatments for autism," Mazmanian added.
Using the co-occurrence of brain and gut problems in ASD as their guide, researchers at Caltech used a mouse model of autism that produces the core behavioural symptoms associated with autism in the offspring.
Using this mouse model, the team then revealed that the ASD-like behaviours were linked to alterations in bacteria living in the animals' guts. What's more, when the team treated the mice with the experimental probiotic Bacteroides fragilis, a number of the behavioural abnormalities including anxiety-like behaviour largely went away.
"The B. fragilis treatment alleviates GI problems in the mouse model and also improves some of the main behavioral symptoms," said Hsiao. "This suggests that GI problems could contribute to particular symptoms in neurodevelopmental disorders."
With the help of clinical collaborators, the researchers are now planning a trial to test the probiotic treatment on the behavioural symptoms of human autism. The trial should begin within the next year or two, said Patterson.
The researchers stressed that much work is still needed to develop an effective and reliable probiotic therapy for human autism—in part because there are both genetic and environmental contributions to the disorder, and because the immune-challenged mother in the mouse model reproduces only the environmental component.
"Autism is such a heterogeneous disorder that the ratio between genetic and environmental contributions could be different in each individual," said Mazmanian. "Even if B. fragilis ameliorates some of the symptoms associated with autism, I would be surprised if it's a universal therapy—it probably won't work for every single case."
Published online ahead of print, doi: 10.1016/j.cell.2013.11.024
"Microbiota Modulate Behavioral and Physiological Abnormalities Associated with Neurodevelopmental Disorders"
Authors: Elaine Y. Hsiao, Sara W. McBride, et al
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