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Scientists have induced the distinctive signs of autism in mice by giving them fecal transplants of humans with the disease.
The experiments were designed to test whether the communities of intestinal microbes discovered in autism play a role in their symptoms, an idea that is gaining ground among researchers.
In this study, animals transplanted into the feces of children with autism became less sociable, less vocal, and developed repetitive behaviors. In contrast, the procedure did not affect genetically identical mice that had undergone non-autistic transplantation.
Sarkis Mazmanian, a microbiologist who led the project at the California Institute of Technology, said that although intestinal microbes do not seem to cause autism, the findings opened up the prospect of new treatments for some of the most common symptoms of the disease.
"This could potentially allow microbiome-based interventions to be effective in autism," he said. "We have identified particular organisms and products of these organisms that cause symptoms in mice, but we do not know if they also cause symptoms in humans."
To perform the faecal transplants, the researchers introduced a known amount of human stool into a tube located in the stomach of the recipient mouse. The animals were then tested to ensure that the microbes present in the stool had colonized the intestine.
The human gut houses billions of insects. In exchange for moisture, heat and nutrition, microbes help digest food, form the immune system and control metabolism. The populations of intestinal microbes are different according to their diet, their lifestyle and their genetics, but studies have shown particular differences in people with autism.
Writing in the journal Cell, scientists describe how they used a tracking system to monitor the level of socialization of mice after fecal transplantation. They also recorded the frequency with which animals buried logs placed on wood chips in their cages. Finally, they used ultrasound microphones to listen to creature communications.
Mice transplanted from autistic children did not struggle, grow, or sniff as much as the control group of mice, which had transplants of non-autistic people. Neither have they produced so much ultrasonic squeaks. And while control mice could bury one or two marbles then move on, mice with autism-related microbiomes continued, indicating repetitive behavior.
Autism affects about one in 60 people and tends to be diagnosed when children show deficits in their social and verbal interactions and display repetitive behaviors such as clapping, rotation, and fluttering. "We were able to see the three main features of autism replicated in mice," said Mazmanian.
Tests on mice with autism-related microbiomes revealed changes in gene expression in the brain and low levels of certain metabolites in the body, including two substances called taurine and 5-aminovaleric acid , or 5AV. In later experiments, the researchers administered taurine and 5AV to strains of mice naturally exhibiting behavior similar to that of autism, and found that their repetitive behavior and their social skills were improved.
Gil Sharon, the first author of the study, said that while human trials might one day determine whether specific bacteria or their products can help people with autism they may not happen quickly. "There is still a lot of work to be done before we can say that we are ready for testing on human beings," he said.
"We do not want to give false hope to parents, children and loved ones," added Mazmanian. "We have not solved the problem. All we have done is present a new potential strategy that needs to be tested on people. This is the beginning of what could ultimately be a therapy for people with autism, but we are certainly not there yet. "
Last month, researchers at Arizona State University announced that stool transplants had nearly halved the symptoms of autism in 18 children. Two years after the intervention, the number of children considered to have "severe" autism had dropped from 83% to 17%.
Jeremy Nicholson, Vice Chancellor of Health at Murdoch University in Perth, Australia, said that the California study was impressive, but he doubted that it was possible to treat the symptoms autism with microbes or pills based on the substances that they produce. "Microbiomes are very diverse in humans, so there is no one-size-fits-all solution. [treatment]. That's why probiotics work on some people and not on others. We need to understand the mechanism behind this situation and then determine if parts of this network are pharmaco-pharmaceuticals. "
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