Two fascinating new studies are shedding light on the association between the gut, the brain, and autism. The new research reveals how gastrointestinal problems can be triggered by the same gene mutations associated with autism, and a striking mouse study has demonstrated how a fecal transplant from humans with autism can promote autism-like behaviors in the animals.

One of the more intriguing areas of microbiome research is the growing connection between gut bacteria and autism. Several recent, albeit small, studies have revealed behavioral and psychological symptoms of autism in children can be improved using fecal transplants from healthy subjects. Exactly how the microbiome could be influencing autism symptoms is still unclear but one new study, led by researchers from Caltech, has strengthened this intriguing gut-brain hypothesis.

The research began by taking microbiome samples from human subjects, both with and without autism, which were then transplanted into germ-free mice. The results were striking, with the animals receiving gut bacteria from human subjects with autism displaying hallmark autistic behaviors such as decreased social interactions and increased repetitive behaviors. The mice administered with gut bacteria from non-autistic human donors did not display these behavioral symptoms.

While affirming surprise at how profound the behavioral effects were in the mice receiving the microbiome transplants from autistic subjects, Gil Sharon, first author on the new study, is quick to note that this research does not imply gut bacteria explicitly causes autism. Instead the research suggests the microbiome more likely interacts with a variety of other factors to potentially enhance the severity of autistic symptoms in an individual subject.

"Our study shows that the gut microbiota is sufficient to promote autism-like behaviors in mice," says Sharon. "However, these findings do not indicate that the gut microbes cause autism."

Further homing in on what genetic or metabolic changes were brought on by the fecal transplants, the researchers discovered distinct alterations in the brains of the autism-influenced mice. As well as discovering alterations in gene expression within the brains of the autism-influenced mice, two key metabolites were found in notably lower volumes: 5-aminovaleric acid (5AV) and taurine.

Following this, the researchers looked at whether delivering 5AV and taurine supplements would reduce behavioral symptoms in mice engineered to display autism-like characteristics. The results were positive, with the supplements reducing autism-like behaviors in the mice. Sarkis Mazmanian, another researcher on the project, says these results do not mean targeting those particular metabolites will immediately translate to improvements in human subjects.

"There are many factors that make autism more complicated in humans than in mice," says Mazmanian. "In mice, we can model the symptoms of the disorder but not reproduce it. However, this research provides clues into the role that the gut microbiota plays in neural changes that are associated with ASD. It suggests that ASD symptoms may one day be remedied with bacterial metabolites or a probiotic drug."

Adding to the gut-brain connection in autism, another newly published study from an international team of researchers has revealed a number of gene mutations known to be associated with neurological alterations related to autism have also been found to directly cause gastrointestinal dysfunctions.

"Up to 90 percent of people with autism suffer from gut issues, which can have a significant impact on daily life for them and their families," says Elisa Hill-Yardin, an investigator on the project from Australia's RMIT University. "Our findings suggest these gastrointestinal problems may stem from the same mutations in genes that are responsible for brain and behavioral issues in autism."

The study specifically homed in on one particular gene mutation, dubbed neuroligin‐3 R451C. Prior research from 15 years ago revealed this particular gene mutation as playing a critical role in altering brain function in some autism sufferers. The new study discovered this particular mutation also affects a number of gastrointestinal functions, including disrupting gut contractions and altering the behavior of the enteric nervous system, a massive mesh of neurons located in our gastrointestinal tract.

Hill-Yardin suggests this discovery affirms how interconnected the gut and brain are, and how future autism treatments need to understand this fundamental connection.

"We know these microbes interact with the brain via the gut-brain axis, so could tweaking them improve mood and behavior? While this wouldn't reverse the gene mutation, we might be able to tone down its effects, and make a real difference in the quality of life for people with autism and their families," says Hill-Yardin.

While both of these new studies are still quite a way off presenting anything approaching a human clinical treatment, they do add to a growing body of evidence connecting the gut microbiome, the brain and autism.

The mouse fecal transplant study was published in the journal Cell.

The autism-gut gene study was published in the journal Autism Research.

Source: CalTech/RMIT