Autism: Whole Body Disorder

Researchers probe link between autism and gastrointestinal problems

Gut bacteria could play role in disease, brain development


The forest and the gut are both thriving ecosystems that exist in a delicate balance, explains MacFabe, a neuroscientist and director of the Kilee Patchell-Evans Autism Research Group at the University of Western Ontario. Disrupt that balance and it can wreak havoc on the landscape and on human health.
In the past decade, an explosion of research on the microbiome, including the gut, reproductive tract and respiratory system, has started to reveal its long overlooked role. Scientists are uncovering how gut microbiota contributes to diseases ranging from irritable bowel syndrome to colon cancer, obesity and arthritis.
MacFabe is among those investigating its potential role in autism. Since 2003, his group has been exploring whether specific bacteria or an imbalance in gut microbes — provoked by infection, environmental toxins, repeated antibiotics that kill off good bacteria as well as the bad, or certain food sensitivities — may contribute to autism in some children.
A central question is “can bacteria alter brain development and function?” he explains.
A potential gut-autism connection is complex, controversial and not well understood. Many physicians are skeptical and caution that research is in the early stages. But MacFabe’s presentation bringing together two of the hottest topics in medical research is a sign it is starting to garner attention beyond the lab.
There are several factors driving interest in autism and the gut. Rates of the neurodevelopmental disorder are soaring, with one in 88 children currently diagnosed, versus one in 150 in 2000, and up 600 per cent in the last 20 years.
For years, research has focused primarily on unravelling its genetic roots. So far genes that have been identified account for 10 to 20 per cent of cases. But there’s an increasing consensus that genes don’t tell the whole story and the culprit is likely a combination of environmental factors and genetics.
“Genes may lead to vulnerability — they may ‘load the gun’ — but so much of the time it’s environment that ‘pulls the trigger,’” Boston pediatric neurologist Dr. Martha Herbert writes in her The Autism Revolution2012 book The Autism Revolution, which also looks at the gut and immune systems of autistic children.
Some scientists are eyeing the gastrointestinal tract as one of the possible culprits.
At the same time, approaches to autism, which varies in severity and causes a range of problems with a child’s communication, social interaction and behaviour, have evolved.
It has long been considered a brain disorder. But more experts like Herbert now consider it a complex “whole body” disorder often accompanied by a range of medical issues, including sleep problems, seizures, metabolic and immune disorders. Chief among them are gastrointestinal problems like chronic constipation, abdominal pain, bloating, reflux and diarrhea, which often go hand in hand with extremely picky eating habits and cravings.
Digestive problems have been reported in children with autism since Leo Kanner first gave the disorder its name in the 1940s. Yet 60 years later, both the frequency and cause are difficult to measure.
“Most of us are going with a figure of 30 per cent,” says Dr. Wendy Roberts, developmental pediatrician at Holland Bloorview Kids Rehabilitation Hospital in Toronto and co-director of the autism research unit at the Hospital for Sick Children.
But she notes data is difficult to collect and cause and effect are hard to tease apart, especially when non-verbal children cannot voice their discomfort. Kids with autism often don’t tolerate a range of textures or tastes and have cravings for specific foods. So Roberts says it’s tough to know whether poor eating habits lead to poor nutrition, digestive difficulties and lack of exercise associated with low energy or muscle tone, or whether those are part of the autistic wiring.
2010 papers published in the journal PediatricsTwo landmark 2010 papers published in the journal Pediatrics finally acknowledged the significance of gastrointestinal problems in autistic children, which can be frequent and debilitating, and urged physicians to treat them seriously.
But the panel of experts noted that the “prevalence and best treatment of these conditions are incompletely understood.”
Last year,another Pediatrics paper reflected the lack of conclusive data, noting that GI problems are estimated to affect between nine per cent and 90 per cent of autistic children. The authors noted there is emerging and relevant evidence related to the gut-brain connection and changes in gut microflora, although it is unclear whether those contribute to autism or are simply coexisting conditions.
Roberts says medical data from the registry of 5,500 children seen through the Autism Treatment Network (ATN) will help shed light on prevalence and best practices for treatment.
The network of 17 sites — including two in Toronto and Edmonton — was launched in 2003 by the U.S. advocacy powerhouse Autism Speaks to research and treat common medical problems associated with autism. Roberts is co-lead of the Toronto ATN.
Last year, Autism Speaks launched an annual conference to look at the range of health issues called “Treating the Whole Person with Autism,” which attracted more than 400 people.
Treatment is a critical issue because gut pain and discomfort can have a huge impact on behaviour, especially when children can’t communicate what’s wrong. It can also interfere with behavioural therapy, affecting a child’s attention and ability to learn.
Understanding how specific bacteria or the wrong mix of microbes may contribute to both the symptoms and the cause of autism in some children is another question.
At the Beijing Genomics Institute in China, where the DNA of 10,000 children with autism is being sequenced to identify genetic markers, there are plans for initiatives looking at the microbiome, spokesperson Bicheng Yang confirmed in an email. But BGI has nothing to report yet, she said.
Two years ago, Autism Speaks awarded a $770,000 grantAutism Speaks awarded a $770,000 grant for research into the biological mechanisms of gastrointestinal disorders in autism that will include the role of gut bacteria.
Last summer, Autism Canada sponsored a scientific symposium on the gut-autism connection.
MacFabe is among a handful of Canadians exploring the topic. In 2007, his research group drew attention for discovering that high levels of a short chain fatty acid called propionic acid, produced in the gut, caused symptoms similar to autism in rats, including anti-social and repetitive behaviours. The compound is produced by certain gut bacteria that have been found in elevated levels among children with autism. And MacFabe says excess levels are also produced by some children when they eat carbohydrates and sugars, which many commonly crave. The theory is that those chemicals may produce toxins that are absorbed into the bloodstream and carried to the brain, affecting behaviour.
“Although promising, such studies need replication in greater numbers of patients,” said a study published last October in Nature. The paper, which reviewed the latest findings on how gut microbiota affect brain and behaviour, said more work needs to be done to prove an association between autism and changes in gut bacteria and whether those changes lead to the gastrointestinal, behavioural and cognitive symptoms in autistic children.
Gut microbes in children with autism are also intriguing to microbiologist Emma Allen-Vercoe at the University of Guelph, who recently launched a project into what she describes as “a relatively understudied section of the autism research field.”
Allen-Vercoe’s lab contains a simulated steel-and-glass gut known as the Robogut, which allows her to grow previously uncultured bacteria that can only survive in environments without oxygen, and to cultivate entire microbial “communities” to study how bacteria function in relation to one another.
She plans to study the gut ecosystems of children with autism and compare them to a control group. Identifying specific bacteria and by-products that cause gastrointestinal problems will also drive further research into whether the gut microbial system is a cause, effect or unrelated to autism.