A leading scientist sets out to prove that gluten and a leaky gut may be causing 20 percent of autism disorders. Reprinted from Allergic Living magazine .
Mute and truculent, the boy sat across from Dr. Alessio Fasano. His parents had brought the 5-year-old to see the pediatric gastroenterologist at the University of Maryland because of he suffered from bloating and other gastrointestinal problems. But the child had autism spectrum disorder and the only way he could express the discomfort he felt was through violence, through throwing things and pounding his little fists.
It was the mid-1990s. Fasano, who’d recently moved to Baltimore from Italy, gently drew the boy’s blood to test for antibodies linked to celiac disease, an autoimmune condition in which the body virulently rejects gluten, a protein in wheat, barley and rye products. When the test, and later an endoscopy, both proved positive, he prescribed the only treatment for the disease: a gluten-free diet.
Over the next six months, the boy transformed in such dramatic fashion that his speech therapist was spurred to write Fasano a letter. “What did you do?” she asked. “I’ve been treating him for three years and couldn’t get two words out of him. Now, he doesn’t stop talking!”
For Fasano, now head of the university’s Celiac Disease Center and a star in the world of celiac research, the solution had been simple.
“It was like this boy was living in a parallel world, trying to communicate with others through a thick veil,” he says. “He did not have to make up developmental milestones so much as have that veil lifted. Once it was gone, there was no stopping him.”
While few turnarounds are as extreme as this boy’s, the case does demonstrate how the body can react to gluten in severe and unexpected ways, far beyond common symptoms such as diarrhea, constipation and stomach bloat.
His interest piqued, Fasano reviewed small studies of gluten’s association with autism and keenly observed his own patients for patterns. This led him to the preliminary observation that a gluten-free diet may help about 20 per cent of the children with autism spectrum disorder or ASD. This is the catch-all term used for mysterious developmental conditions that range in severity and are characterized by varying degrees of social deficits and repetitive behaviors.
Not that the kids with a response to gluten have undiagnosed cases of celiac disease; rather, Fasano suspects gluten sensitivity . This is a relatively new medical diagnosis with a wide range of symptoms similar to those seen in celiac disease, but without untreated celiac’s association with osteoporosis, infertility and other serious health issues.
“We can’t help all kids with autism,” Fasano cautions of the gluten and ASD research. “But that help, when it comes, can be pretty dramatic, not just for the child but for the whole family.”
Next page: Investigating the ‘leaky gut’
To prove his theory, Fasano needs tests on a much larger scale. And that’s why, 15-odd years after first meeting that 5-year-old boy, he is a lead scientist in two studies that are exploring the links between general gastrointestinal dysfunction and ASD.
Investigators from the Celiac Disease Center, the University of California at Davis and the California Institute of Technology are now studying the biological makeup of the guts of children with ASD. They’ll try to confirm the suspected biomarkers of gluten sensitivity in these kids and, if successful, they’ll put the kids with those biomarkers on gluten-free diets. Then they’ll observe, to see what happens to their symptoms.
In the second study, the scientists are working with mice – which are given genes that make them behave in a manner akin to autism. The researchers will use these mice to test a therapy that bombards the gut with probiotics. The idea is to figure out the role of microorganisms involved in gluten sensitivity and, ultimately, their role in ASD. If successful, this could lead to a non-medicinal therapy that involving probiotics and gluten-free diets.
There is so much confusion surrounding ASD. Fasano has tallied up more than 50 treatments being practiced that are either scientifically unproven or debunked. They range from the prescribing of antidepressant drugs to enclosing kids in hyperbaric chambers, foregoing vaccinations for common childhood diseases and chelation – the removal of heavy metals from the body.
“Amongst all these treatments, adjusting a diet so it does not contain certain elements seems the most innocent of all,” he says. “But there should be scientific research to back up such a decision.”
The stakes for research success are high, since at least one in 110 children in the United States is thought be on the spectrum, and living with its profound effects. That’s a staggering 600 per cent increase over the past two decades, with treatment and support costs in the United States alone running beyond $35 billion a year.
Improved diagnoses can only partly explain the ASD phenomenon. For years, autism was only considered a neurological condition (or conditions), but then scientists like Dr. Stanley Finegold of UCLA began studying the role of the gut and gut bacteria.
Today, Fasano and his colleagues are moving that research forward to a related but different question: might it not just be the gut, but a “leaky gut” that explains at least a significant part of this disordered spectrum?
Fasano is exploring the links between a genetic predisposition for ASD, environmental triggers such as nutrients and “leaky gut syndrome,” which he knows occurs in celiac disease and, he suspects, also in gluten sensitivity.
The syndrome occurs when the body detects gluten and releases zonulin, a protein which makes the intestine more permeable or “leaky”, allowing certain molecules, including gluten, the dairy protein casein and other proteins to pass through the cells that line the intestines. This leads to an immune response and gut inflammation.
Fasano ascribes to a theory that some inflamed cells in the gut make it through the bloodstream to the brain, causing ASD in the group of children with the genetic predisposition.
At least half of kids on the spectrum are thought to have some kind of gastric issue. But like that early patient of Fasano’s, many of the children do not speak, which leads them to express distress in other ways. Some will scream or whine, some are frequent throat-clearers, others eat constantly, while still others can’t sleep through the night. And many parents, desperate for something, anything that might help, place their children on diets free of gluten and casein, even though the evidence to support this is only anecdotal.
It is time to change that, according to Dr. Clara Lajonchere, the vice-president of clinical programs for Autism Speaks , the world’s largest autism science and advocacy group which is funding one of the two new research studies. (The other is financed by the U.S. Department of Defense, which funds a number of initiatives linked to the health of military personnel and their families, including autism.)
Scientists need to sift through the often passionate testimonials and tales, says Lajonchere, to prioritize the issues for families and to rigorously test, measure and weigh the benefits of alternative treatments against those of traditional medicine.
Next page: Shedding light and moving to treatment
“When it comes to treatments for ASD, we know that one size does not fit all,” she says from her office in Los Angeles. “Some kids with GI problems may respond to treatment and some may not. But there will be incredible value added if we can scientifically identify a subset of kids who can be treated this way.
“And once we start to understand what’s going on in their guts, it may shed light on the underlying biology of the syndrome and lead us to what’s going on in the brain and nervous system.”
The research of Fasano and his colleagues is complicated because ASD is just that – a spectrum disorder – hard to pin down because it is not a single, defined medical condition. Its causes are thought to be myriad, which is why Fasano says that “we have to walk the same route that each of these children took to arrive at ASD as their final destination. By doing so, we aim to help these same kids turn around and walk back, like following bread crumbs.”
This work is a natural extension of Fasano’s ground-breaking research into celiac disease, because he suspects that no matter the cause, leaky gut syndrome will inevitably lead to diverse health problems because all sorts of bad things get through to the rest of the body.
“I believe in serendipity,” Fasano says. “Word spread that I was working on leaky gut syndrome and Autism Speaks invited me to talk about how impaired barriers may function in autism,” he says.
“I thought, ‘Wouldn’t that be interesting?’ I don’t see many kids with autism, but in some of the kids brought to us with gluten sensitivity and behavioral issues, I can definitely see a difference. They become more verbal. Some are almost indistinguishable from kids without such issues.”
“The key,” he continues, “is to figure out who has gluten sensitivity and a leaky gut and not just randomly treat all ASD patients,” he says. That’s why he and other medical researchers need to identify better biomarkers for gluten sensitivity, as has been done for celiac disease.
Fasano’s first challenge is to identify a specific combination of “bad bacteria” that causes the leaky gut, which in turn leads to inflammation and, finally, to ASD. If such a combination exists, next he wants to track the bacteria’s pathways to identify metabolites that can be used as biomarkers, or red flags, in the development of the disorder. Finally, with pathways mapped and red flags marked, he wants to try to repair the intestinal barrier by manipulating the bacteria.
The goal of the research is twofold: to identify kids at risk of developing ASD in the first place and, for those who already have it, to reverse it as much as possible.
“The gut is not like Las Vegas. What happens in the gut does not stay in the gut,” he says. “Just like in celiac disease, some of these immune cells will migrate to other areas of the body, including the brain.” And the few autopsy reports he has seen of children with ASD indicate that they had inflammation in their brains.
“How did it happen?” he asks. “How can we prevent it? That’s what we want to understand.”