New research shows young children with a family history of autism spectrum disorder have a different mix of bacteria living in their intestines.
An autistic person’s brain works differently to most people. This can mean they find it hard to communicate and interact with others and may struggle to understand how people think or feel.
Young children with an older sibling who is autistic are at least 20% more likely to be diagnosed with autism themselves. New research shows these children have different bacteria residing in their gut in the first few months of life compared to those without an autistic sibling.
Over the last two decades, there has been increasing evidence that these intestinal microorganisms can produce chemicals that influence the way the brain develops. This has consequences for emotional behaviour and brain function. These 'microbial metabolites' contribute to a communication network called the microbiota-gut-brain axis.
Prof Jonathan Swann, from the NIHR Southampton Biomedical Research Centre, jointly led the study. The results, published in Translational Psychiatry, could improve our understanding of how the brains of autistic children develop differently, highlighting potential targets for future treatments.
Investigating how autism develops
Autism is considered to be influenced by various factors, but it’s thought a major contributor is the bacteria living within a child’s gut.
Trillions of microorganisms, including bacteria, viruses, and fungi, are estimated to live in our intestines. This community is collectively known as the gut microbiota. It starts to develop from birth, rapidly maturing across the first few years of life. During this period it plays a key role in health and development. It contributes to digestion, metabolism, immune maturation and brain development.
The researchers investigated how the gut microbiome might influence brain development in autistic children. They followed infants from five months of life, before any behavioural differences can be identified, to three years in age.
They compared the gut microbiota of 16 children with an autistic sibling, who are more likely to be autistic themselves, to that of 19 children who did not have an autistic sibling. All children lived in and around Stockholm, and were part of the ongoing long-term Early Autism Sweden (EASE) project.
The researchers investigated how their microbiome changed over time. They did this by analysing the children’s faecal samples at the ages of five months, 10 months, 14 months, two years and three years.
They assessed the children’s development at five months, using the Mullen Scales of Early Learning (MSEL) test, and again at three years. They also checked for signs of autism at age three, using the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2).
Different patterns
At five months, they found differences in the bacteria of the children's stools with an elevated likelihood of autism compared to those with a low likelihood. Children with an elevated likelihood had less bifidobacteria and more clostridia. Feeding practices (breast, formula, mixed feeding) were similar for all infants, so dietary variation did not influence the results.
The researchers measured the metabolites present in the stool samples. They found gamma-aminobutyric acid (GABA) peaked in children without a family history of autism at five months, before progressively declining with age. GABA is a key neurotransmitter, or chemical messenger, with an important role in neurodevelopment. Intriguingly, children with an autistic sibling did not have such a peak. Instead, they had consistently low levels of GABA in their stools across the first three years of life.
Laboratory work showed bifidobacteria were able to produce GABA, while clostridia consumed it. This suggests it was the bacteria that were driving the differences in the amount of GABA present in the infant gut.
There were no behavioural differences between the two groups at five months of age. But by three years, the children with autistic siblings had significantly lower MSEL and ADOS-2 scores. None of the children were diagnosed with autism during the study. However, this was to be expected, as most children in Sweden are diagnosed after the age of five.
Prof Swann, Professor of Biomolecular Medicine at the University of Southampton, said:
“These are extremely interesting results, which reveal important new insights into how the intestinal microbiota of children develop and produce neuromodulatory signals and how these vary between infants with different familial histories of autism.”
“The first three years of a child’s life are a critical period for both brain development and the acquisition and maturation of their gut microbiota. This work demonstrates how the two processes are intricately linked, and further highlights how we evolved in the presence of our gut microbiota.”
“The microbiota is an attractive target because it is both accessible and amenable to dietary modulation. Work is now underway to explore how we can leverage the microbiota to promote favourable development of the brain. This includes the use of bifidogenic prebiotics and bifidobacteria-containing probiotics.”