Research confirms intestinal-brain connection in autism

People with autism often suffer from intestinal problems, but nobody knows why. Researchers have now discovered that the same genetic mutations – both in the brain and in the intestines – could be the cause.

The discovery confirms a link between the nervous system and the intestines and the brain in autism, opening a new direction in the search for potential treatments that could alleviate behavioral problems associated with autism in targeting the intestine.

Lead researcher Elisa Hill-Yardin, RMIT University, said that scientists trying to understand autism have long been looking into the brain, but that links with the gut have only been explored recently. .

"We know that the brain and intestines share many of the same neurons and now we have confirmed for the first time that they also shared autism-related genetic mutations," Hill-Yardin said.

"Nearly 90% of people with autism suffer from intestinal problems, which can have a significant impact on their daily lives, as well as those of their families.

"Our findings suggest that these gastrointestinal problems could stem from the same mutations in the genes responsible for the brain and behavioral problems of autism.

"It's a whole new way of thinking – for clinicians, families, and researchers – and it expands our horizons in seeking treatments to improve the quality of life of people with autism."

The autism gene and the intestine-brain link

The study revealed a genetic mutation that affects neuronal communication in the brain. This disease, which was the first to be identified as a cause of autism, also causes bowel dysfunction.

The research brings together new results from pre-clinical animal studies and unpublished clinical work from a landmark study conducted in 2003 by Swedish researchers and a French geneticist.

The work of Professors Christopher Gillberg (University of Gothenburg), Maria Råstam (University of Lund) and Thomas Bourgeron (Pasteur Institute) were the first to identify a specific genetic mutation as a cause of the neurodevelopmental disorder.

This mutation affects communication by modifying the "velcro" between the neurons that keeps them in close contact.

While the 2003 study was focused on identifying the genetic basis of autism, Gillberg and Råstam also took detailed clinical notes on the brothers' important gastrointestinal problems.

Researchers from RMIT's Ax-Gut-Brain Axis team have relied on this clinical work with a series of studies on the function and structure of the intestine in mice with the same mutation. gene "velcro".

They discovered that this mutation affects:

• intestinal contractions
• the number of neurons in the small intestine
• the speed at which food passes into the small intestine
• responses to a neurotransmitter essential in autism (well known in the brain but never identified to play a major role in the intestine)

Associate Professor Ashley Franks (University of La Trobe) also found significant differences in intestinal microbes in mice with and without the mutation, even though both groups were conserved in identical environments.

Although this specific "velcro" mutation is rare, it is one of more than 150 autism-related genetic mutations that alter neuronal connections, Hill-Yardin said.

"The link we confirmed suggests a broader mechanism, indicating that mutations that affect connections between neurons could be at the root of intestinal problems in many patients."

New horizons of research on the intestine-brain axis

Hill-Yardin, senior scientist for the ARC Future program and vice-chancellor at the RMIT School of Health and Biomedical Sciences, said the work identified a new target for the development of therapies specifically designed to act on neurotransmitters in the intestine.

"We have also identified the need to better understand how existing anti-autism drugs that target neurotransmitters in the brain affect the intestine," she said.

"Another promising avenue for future research is to study the link between gene mutations in the nervous system and microbes in the intestine.

"We know that these microbes interact with the brain via the gut-brain axis, so could their modification improve mood and behavior?"

"Even if it does not reverse the mutation of the gene, we could perhaps mitigate the effects and make a real difference in the quality of life of people with autism and their families."