The genetic risk for autism has always existed, but in the last 40 years the prevalence has risen dramatically – and not in any one location, but across all developed nations. Many researchers are looking to identify the trigger and, as a gastroenterologist and neurologist, Dr. Emeran Mayer is following the trail of evidence that points to the microbial composition of the digestive system and its relationship to the brain. The gut microbes of those with autism differs from people who aren’t on the autism spectrum, but so far many of the studies have not been sufficient to draw solid results. Dr. Mayer runs through one of the more compelling studies and explains how a yet unapproved strain of probiotic may be the answer to the decreasing the incidence of autism in the future. Dr. Emeran Mayer’s most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health.

Dr Emeran Mayer’s most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health

.

Emeran Mayer: Autism is both a devastating problem and it’s still a puzzle largely what causes or what has been causing the dramatic increase in the prevalence of this disease in the last 40 years or so. So it’s almost like an exponential increase. Part of that is really due to better diagnosis and the diagnostic criteria. But a lot of people think that something in our environment has played a role in causing this increase. And it’s worldwide. It’s not just in North America. It’s in Asia, it’s in Europe. So something environmental. The genes, the genetic risk factors for autism have obviously always been there but something else must have triggered it. So some people think it’s something in the diet and that is possible. It could also be something what we do to our gut microbes. So the use of antibiotics, the obsession with keeping things more and more sterile from the day we’re born, you know, throughout our lifetime.

So people have thought about this as potentially a change in microbial composition, diversity inside of us are a cause of this. There’s many observations that link the brain and the gut in autism. Clinically the majority of autistic children have digestive problems – constipation, abdominal pain, discomfort. Part of that is most likely due to the diet, the unique diet that autistic children self-select for. Many things are excluded from the diet that we normally would like fiber, fermented foods. And so it’s very possible that that plays a role. And there are people that have thought about this why do kids select such a diet. It seems to have to do a lot with the texture of foods. So very unique disturbance in the sensitivity for the texture, not so much for the content. So things that are soft are much preferred over crunchy and chewy things. And then, you know, people have started to look at the microbial composition. So they looked at the gut microbes in fecal samples from patients with autism and have found abnormalities.

The problem is most of those studies are small. They’re often not well controlled. We now understand that autism is a spectrum, autism spectrum disorder. And it probably contains several different subsets of patients. So if you just take a small number of patients, measure their gut microbes it’s, you’re likely to pick up variable patterns because it’s not a homogeneous group of patients. And the last thing that’s happened which has really drawn a lot of attention to it has been a study published a couple of years ago by a group at Cal Tech in California which showed that in an animal model of what’s called maternal immune activation – so where the mother undergoes an infection or immune activation during pregnancy. And then the offspring, the mother’s offspring shows altered social behavior. And there’s various tests that have been taken as animal behavior equivalents to human autism. Always, you know, a big chunk from something, from animal behaviors to something as complex as all the disturbances in autism. But that has received a lot of attention because in these animals that have these behaviors they have an altered gut microbial composition, produce different metabolites, particularly one metabolite that’s also been found in human patients. And they have a leaky gut. So they have immune activation in the gut and by treating these animals with – that’s the most intriguing. By treating them with a probiotic which is called B. fragilis, the investigators were able to reverse many of those behavioral changes and the gut abnormalities in these mice.

So this has triggered a tremendous interest now. There’s efforts underway to produce this probiotic and make it acceptable for human use. So it’s not a probiotic that you currently can get in your yogurt or cheese. It has to be approved. It has to be cultured. But clinical trials will happen in the next couple of years that will test this hypothesis. Can you actually by influencing the microbial composition reverse some of the changes either in terms of the gut dysfunction or cognitive and social interaction of these patients. One would assume that in humans the earlier you could start that therapy after delivery – this is clearly a developmental disorder that starts initially almost with imperceptible changes in the newborn and then gradually becomes clinically obvious. The earlier you could start this treatment, the more likely it would be beneficial. So autism in many ways is the prototypic brain-gut microbiome disorder. So this model is almost certainly going to lead to a better understanding and breakthroughs and diagnosis and therapy. But there’s still a ways to go.

So probiotic is a microbe with a demonstrated health benefit. So lots of microbes would qualify for this. We have 100 trillion of these microbes inside of our gut so many of those are potential probiotics that if you isolate them, culture them and then give them to humans – and that’s like with this B. fragilis. It’s produced in the context of infections and abscesses strangely. But it has been shown to have many beneficial effects also stimulating the immune system. That effect on autism appears to be different from the one that has been demonstrated earlier from its anti-inflammatory effect on the gut’s immune system. So it does exist. It just doesn’t exist in a form that is currently commercially available or that would be allowed by the FDA that you could put this into humans. So the trial was left to demonstrate the safety which most likely will be shown. But the FDA is fairly strict. Anytime you use a probiotic even the ones that are in commercially available products if you want to prove that a particular yogurt with its microbes is probiotic is beneficial for a disease condition you need to get FDA approval just like for any other drug which is a complex process, a time consuming process. And it’s kind of slowed the progress in this field of identifying microbes with potential health. So new microbes with potential health benefits.