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t m c » p u l s e | a p r i l 2 0 1 9 19 N ot only is there is no cure for autism spectrum disorder, but there is no one-size-fits-all approach to treatment. Individuals with autism spectrum disorder (ASD) struggle by varying degrees to communicate and interact with others. Often, they exhibit repetitive behavior and become agitated when a particular routine or ritual is changed. Symptoms can range from severe to mild and many parents choose a combination of behav- ioral interventions and medication to help control symptoms and associated medical conditions. One in 59 children in the United States is diagnosed with ASD, according to the Centers for Disease Control and Prevention. Currently, no existing therapies completely mitigate the many manifestations of the disorder, but scientists at Baylor College of Medicine may be close to a truly groundbreaking discovery. According to a paper published recently in the journal Neuron, Mauro Costa-Mattioli, Ph.D., and first author Martina Sgritta, Ph.D., have successfully reversed social deficits associated with ASD in mice through a simple, bacterial-based therapy. The unconventional approach has widespread potential for the development of noninva- sive therapies for autism and suggests a future in which the microbi- ome plays a major role in the treatment of neurological conditions. A deeper understanding Research by Costa-Mattioli and Sgritta showed that the adminis- tration of the bacteria species Lactobacillus reuteri led to specific changes in the brain that restored social behaviors in their mice models—mice that are bred to have autism. Previous research by this team and others indicated that Lactobacillus reuteri increased oxytocin levels in the brain, but had not determined the channel of communication by which the microbe affected the brain. "In this research, we determined that the vagus nerve and the oxytocin-dopamine reward system were both necessary for the social behaviors to be restored," explained Sgritta, a postdoctoral associate in the Costa-Mattioli lab at Baylor. "When we cut the vagus nerve, the treatment with the bacteria had no effect. When we pre- vented the oxytocin to bind to its receptors in the specific brain area involved in social reward, the bacteria was not able to have an effect either. So L. reuteri needed both the vagus nerve and the oxytocin receptors to restore the behavior." That deeper understanding of the mechanisms involved plays a critical role in analyzing exactly how the bacteria restored social behaviors in the mice models, since increased levels of oxytocin—also known as the "love hormone"—are related to a boost in sociability. Another key finding of the study relates to the different mouse models the researchers used—each bred for different variations of autism, including genetic, environmental and idiopathic. They dis- covered that no matter the type, the outcome remained essentially the same. "The goal of a treatment right now is to ameliorate the life of a person with ASD," Sgritta said. "What we found was that no matter the origin of the disorder, we were able to correct social behavior through the Lactobacillus reuteri." The bacterium is already commercially available and considered safe—it is often used to treat colic in infants, said Costa-Mattioli, the Cullen Foundation Endowed Chair of Neuroscience and director of the Memory and Brain Research Center at Baylor. "There are no secondary effects and there is no toxicity," he added. While the new ASD research has only tackled social behaviors thus far, the results could extend beyond their original potential. "There are three symptoms which define the disorder: social defi- cit, repetitive behavior and language impair- ment," Costa-Mattioli said. "Through this research, we have only reversed one leg of autism in the mice— the social deficit. But the other two legs, we haven't tested." This research comes on the heels of an up-and-coming field of study focused on the gut microbiome, a group of microorganisms in the gut that breaks down food and protects the body from germs. For scientists already well-acquainted with the latest research, which suggests that the gut microbiome plays a key role in everything from regulating the immune system to influencing neurological processes, the connec- tion between a bacteria species and social behavior doesn't come as a surprise. "The connection is not shocking," Costa-Mattioli said. "What is shocking, though, is that we may end up with a particular strain of bacteria as a way to treat this brain disorder. We have trillions of bugs in our guts, and it may be one of these bacterial species that could be used to ameliorate specific symptoms." Looking to the future The bacterium Lactobacillus reuteri originates in the gut and has been found in breast milk. For the study, the researchers boosted its presence by putting it into the water the mice drank on a daily basis. Interestingly, its prevalence has decreased over the past few decades, especially in highly developed and industrialized countries. "A colleague of mine at the University of Alberta, Jens Walter, has studied the evolution of this bacteria over the years, and, com- paring the gut microbiota of U.S. people and non-industrialized areas, he has discovered that this bacterial strain was not detectable in the gut of westernized human populations, while it was found in the gut of people living in rural communities," Costa-Mattioli said. "So, perhaps diet, or stress, or all these conditions have eliminated this bacterial strain from our gut. If you go and you look at people here in Houston, you will maybe have a hard time finding this bacterium at all. But if you go to native populations or study the microbiome of people from 50 years ago, the probability that you would find it is higher." Is it possible, then, that the disappearance of this bacterium correlates with the increase in diagnoses for ASD? In other words, if Costa-Mattioli and Sgritta's research shows that Lactobacillus reuteri can restore a key symptom of autism in mice, could a lack of Lactobacillus reuteri be a cause of autism? ➟ Facing page: At the Costa-Mattioli lab at Baylor College of Medicine, scientists are studying a potential new therapy for autism spectrum disorder. Top right: Martina Sgritta, Ph.D., is a postdoctoral associate in the lab.