Gut-brain link to autism confirmed: Study identifies similar gene mutation in both the brain and gut

05 Jun 2019 --- Autism is linked to similar gene mutations found in both the brain and the gut, according to a new study from the Royal Melbourne Institute of Technology (RMIT) in Australia. The vast majority of people with autism suffer from gut problems and the reason behind this was, until now, unknown. The study findings confirm a gut-brain nervous system link in autism, opening a new direction in the search for potential treatments that could ease behavioral issues associated with autism by targeting the gut.

Scientists trying to understand autism have long been looking into the brain, but the links with the gut nervous system have only been recently explored, says RMIT Chief Investigator, Associate Professor Elisa Hill-Yardin. “We know the brain and gut share many of the same neurons and now for the first time we’ve confirmed that they also share autism-related gene mutations.”

“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,” she notes. “Our findings suggest these gastrointestinal problems may stem from the same mutations in genes that are responsible for brain and behavioral issues in autism.”

Hill-Yardin goes on to say that the findings, which are to be published in Autism Research, offer a whole new way of thinking about the matter for clinicians, families and researchers. In addition, they broaden the scientific community’s horizons in the search for treatments to improve the quality of life for people with autism.

Gene mutation related to autism also linked to gut dysfunction
The study identified a gene mutation that affects neuron communication in the brain, which was the first to be identified as a cause of autism. The same gene is also responsible for dysfunction in the gut. The research combined new results from pre-clinical animal studies with previously unpublished clinical work from a landmark 2003 study led by Swedish researchers and a French geneticist.

Credit: Roman YanushevskyProfessor Christopher Gillberg (University of Gothenburg), Professor Maria Råstam (Lund University) and Professor Thomas Bourgeron (Pasteur Institute) followed two brothers with autism and were the first to identify the specific gene mutation as a cause of the neurodevelopmental disorder.

This mutation affects communication by altering the connection (“velcro”) between neurons that keeps them in close contact. While the 2003 study primarily focused on identifying the genetic basis for autism, Gillberg and Råstam took detailed clinical notes of the brothers’ significant gastrointestinal problems.

The RMIT researchers built on this clinical work with a series of studies on the function and structure of the gut in mice that have the same “velcro” gene mutation.

The team found this mutation affects:

• Gut contractions.
• The number of neurons in the small intestine.
• The speed that food moves through the small intestine.
• Responses to a critical neurotransmitter important in autism (well known in the brain but not previously identified to play any major role in the gut).

Collaborator Associate Professor Ashley Franks from La Trobe University, Melbourne, Australia, also found significant differences in the gut microbes of mice with the mutation and those without it, even though both groups were kept in identical environments. 

“While this specific ‘velcro’ mutation is rare, it is one of more than 150 autism-related gene mutations that alter neuronal connections,” Hill-Yardin says. “The link we've confirmed suggests a broader mechanism, indicating that the mutations that affect connections between neurons could be behind the gut problems in many patients.”

New research avenues 
Hill-Yardin says the work identifies a new a target for the development of therapies specifically designed to work on neurotransmitters in the gut. “We’ve also identified that there’s a need to better understand how existing autism medications that target neurotransmitters in the brain are affecting the gut,” she notes. 

“Another promising path for future research is investigating how gene mutations in the nervous system relate with microbes in the gut,” Hill-Yardin adds. “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, it may allow researchers to tone down its effects, and make a real difference in the quality of life for people with autism and their families, Hill-Yardin says.

Previously a study published in the Journal of Autism and Developmental Disorders found that gastrointestinal (GI) distress could be the source of anger, aggression and other troubling behavioral problems in children with autism. While a recent pilot study from Kyoto Prefectural University of Medicine (KPUM) in Japan found that soluble guar fiber may help improve constipation and by extension irritability in children within the autism spectrum.