Gut feeling. scientists say this common microbe Bacteroides fragilis , could help restore normal behavior in mice to mimic autism.
CNRI / Science Photo Library
Many doctors and parents report that their autistic children have particularly serious gastrointestinal problems, such as chronic constipation or diarrhea . These observations have led some researchers to speculate that the diseased intestine contributes to the disorder in some cases, but the scientific data were insufficient. Now, a provocative study claims that probiotic treatment for gastrointestinal problems may reduce autismlike symptoms in mice, suggesting that this treatment could work for humans as well.
The frequency of bowel disease in people with autism varies widely between zero-published studies over 80% -Make it is difficult to establish how widely the two conditions go hand in hand says principal investigator Sarkis Mazmanian, a microbiologist at the California Institute of technology (Caltech) in Pasadena. Overall, however, the evidence seems to point to a connection. Last year, for example, a Centers for Disease Control and Prevention Study of thousands of children with developmental disabilities found that children with autism were twice as likely as children with other types of disorders have frequent diarrhea or colitis, an inflammation of the large intestine.
For many years, Mazmanian and his and his colleagues studied the effects of a nontoxic strain of the bacterium Bacteroides fragilis on diseases such as Crohn's disease, which causes intestinal inflammation and allows potentially harmful substances to pass on the body to escape through the junctions between cells that are normally tight. Although researchers do not understand the mechanism, the bacterium appears to restore the damaged intestine, possibly by helping fill those gaps.
"The fact that we have an organization that repairs the gut makes it a very attractive" tool to check for abnormalities of the gut may contribute to autism, said Mazmanian. To explore this issue, Mazmanian and colleagues at Caltech have used a mouse model of autism is thought to recreate about three messy stamp deficits: lack of social interaction, reduced communication (normally emit mouse ultrasonic chirps birdsonglike), and repetitive behaviors such as grooming compulsive or landfill ball.
The first step of the experiment was to determine whether the mice showed signs of gastrointestinal inflammation or other abnormalities of the intestine, said microbiologist Elaine Hsiao, a postdoctoral candidate at Caltech and lead author of the study. When the mice were 3 weeks, the researchers found that their intestines were indeed like leaky mice that had been treated with a chemical that induces colitis. Next, the researchers tested whether they can reverse the damage by feeding on mice applesauce laced with B. fragilis for a week. A second group of mice that mimic autism and a healthy group of mice ate the apple sauce that does not contain bacteria. The group then waited to see what effect the bacteria would have on rodents intestines. "We did not know what would happen-we hoped the bacteria could survive in the intestine," says Hsiao.
After 3 weeks, the team measured the levels of molecules in the intestine derivatives the blood of rodents and found that the treatment had stopped their intestinal leakage. the number of rodent poop bacteria have shown that although B. fragilis has not established lasting colonies in mice, they "shake the community," micro-organisms, approaching that of normal mice, Hsiao said. After treatment, the mice mimicking autism also resembled their normal peers in two behavioral tests, the authors report today Cell . Pets are no longer compulsively buried balls in their cages and increased their ultrasonic grinding to typical levels. They have not increased their social interactions, however, says Hsiao.
"It really is striking that any treatment, even a transient bacteria could have a lasting impact on behavior," says Hsiao. The most interesting thing about the results, she said, No. no correction of autistic symptoms in mice, but the study provided clues about how the microbial population of the gut can affect the brain and behavior. the researchers found that levels of a substance called 4 -ethylphenylsulfate that is produced by bacteria of the intestine increased 46 times in mice with autistic symptoms, but returned to normal after treatment with B. fragilis . When the team isolated this chemical and injected into healthy mice, the rodents showed anxiety increased, another autismlike symptoms, she said. While the substance did not cause the symptoms observed in the previous experiment, Hsiao said the altered response of animals suggests that the substance may play a role in the disorder. Hundreds of other metabolic byproducts have also changed in amount after B. fragilis was administered and could have an effect, it adds
By demonstrating that the mouse model widely used of autism have gastrointestinal problems, and these problems are associated with behavioral symptoms, new research. "shows us something fabulous," said Betty Diamond, an immunologist at the Feinstein Institute medical research in Manhasset, New York. It warns, however, it would be premature to use B. fragilis or other probiotic treatment as in humans. "We do not really understand" what bacterial species are important or how they colonize the intestine, she said.
Although the results are interesting, the study does not prove that changing levels of microbes and the chemicals they produce one caused behavioral changes observed in mice, says Emanuel DiCicco-Bloom, a neuroscientist at Rutgers University in New Brunswick, New Jersey. "I want to know more about the mechanism "whereby the modified bacteria behavior in mice before starting to translate the results to humans, he said. The group has also not investigated how bacteria affect a normal animal, because the microbes were only administered to mice with autism, he said. It is possible that B. fragilis could have a deleterious effect that the study did not detect, he said. Combined with the difficulty inherent in the extrapolation of human autism conclusions of a mouse, he said, "I think it is less well established than it appears."
" We propose that, after the repair of leaky gut, neurotoxic molecules do not enter the system and cause behavioral abnormalities, "says Mazmanian. But he agrees with DiCicco-Bloom there are other explanations for why the mice changed their behavior for example, "maybe the nerves are activated bacteria in the gut that are in communication with the brain, "he said. After resolving some of these issues, the group plans to launch clinical trials in humans, Hsiao said." We do not want people to start applying this to humans "for now, but "it opens the door to future research" in people.
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