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Getting to the guts of autism

To roughly two million Americans struggling with autism, chronic stomach problems have long been just another side effect. Now, it looks like the issues in their guts could actually be aggravating—or even triggering—their symptoms of autism.

A new arm of autism research has begun to explore the possibility that problems in the gut microbiome—an entire ecosystem of bacteria residing within the digestive tract that is responsible for extracting energy from food—could actually play a role in exacerbating or even causing behaviors and symptoms associated with autism.

While researchers from a variety of disciplines around the world are turning their attention to the stomach, University of Delaware Professor of Chemical and Biomolecular Engineering Prasad Dhurjati is helping to put their work into context.

Microbiologists at UCLA are exploring whether an injected form of antibiotics might change the bacterial populations of the gut in a way that relieves some symptoms of autism. Neuroscientists at the University of Western Ontario are examining the effects that certain byproducts of incomplete digestion can have when introduced to the brain.

In Delaware, Dhurjati has developed a theory that might help connect the dots among the various specialized studies. He published his theory last month in the peer-reviewed scientific journal, Medical Hypotheses.

Dhurjati’s theory describes possible sets of chain reactions that could be delivering toxic inputs and messages from the gut to the brain in people on the autism spectrum.

“Everyone looks at his or her own small piece of the puzzle. Our contribution is not in individual components. What we are trying to see is how all these factors are connected together,” Dhurjati said.

Dhurjati’s approach is grounded in systems biology, a holistic field of study that looks at the way components of the body work together. While a neurologist focuses on the brain, a geneticist homes in on individual genes, and a gastroenterologist addresses the gut, a systems biologist examines all three as interconnected components of the larger biological system of the body.

In recent years, scientists have theorized that the influence of gut flora extends far beyond simple digestion. Gut bacteria have been suspected as accomplices in the hardening of arteries leading to heart disease, in the establishment of autoimmune diseases like rheumatoid arthritis, and in the development of insulin resistance in the onset of diabetes.

The human body plays host to some 3 million microbes, many of which live in the digestive tract. These microscopic residents are so numerous they are thought to exist within their own ecosystem, called the microbiome. In a healthy gut, this bacterial community works together to break down food, regulate metabolic signaling, and orchestrate circadian rhythms.

“One of the things [gut bugs] do is produce proteins or enzymes that break things down. If you are missing some of these microbes, then you are missing some of the breakdown capacity,” Dhurjati said.

The effects of incomplete digestion can not only inhibit the body’s ability to absorb vital nutrients, but potentially result in the build up of toxins that could later travel through the bloodstream to the brain, he said. This is just one of a number of potential pathways outlined by his theory.

Everyone’s microbiome is unique, acquired from a lifetime of experiences. The gut’s first settlers tend to be immigrants from the mother and doctor in the delivery room. Children who are born via cesarean section have different gut bugs than those born vaginally. External inputs can further affect the bacterial community. For instance, antibiotics prescribed to attack infection-causing bacteria can indiscriminately kill beneficial flora in the gut as well.

As in any ecosystem, when once species dies off, another tends to move in and take its place. Recent research has begun to search for correlations between specific gut communities and autistic symptoms.

“We need to be able to absorb our nutrients in order to run our cells and to run our brain cells. Without certain basic nutrients, you don’t make enough neurotransmitters and you don’t produce enough energy to really run your brain properly,” said Martha Herbert, a pediatric neuroscientist at the Massachusetts General Hospital in Boston, an assistant professor of neurology at the Harvard Medical School, and author of the 2012 book The Autism Revolution.

The buzz around this potential connection has spurred her to start collecting diapers from infants at high risk for autism in order to begin her own investigation.

Herbert sees Dhurjati’s paper as a vital stepping-stone in the long path from research to treatments for autism. While she has seen robust data indicating a strong correlation, little has been done to determine a causal link.

To do that, you need a good way to think about the mechanisms through which the gut can affect the brain, Herbert said.

Dhurjati’s paper provides a map of mechanisms that can be studied further to determine that causation.

His theory supposes that incomplete digestion could lead to impaired removal of toxic heavy metals and could change the dynamic of gut bug populations. Surges in particular bacteria could cause gut inflammation, which could lead to tears in the barrier separating the intestine from the bloodstream. Once that barrier has been breached, toxins could hitch a ride directly to the brain. His paper goes on to reveal a complex web of chain reactions like these that could function as pathways from the gut to the brain.

Herbert sees potential in Dhurjati’s theory and the holistic approach of examining multiple interconnections within the entire system. She would like to see the pathways extended a few steps further to explain how toxins could cross the blood-brain barrier and specify how they act on the brain.

“We know that toxins can interfere with a lot of important processes in the brain. From my point of view, that still doesn’t really explain stuff. You really want to measure some difference in the way the brain behaves,” Herbert said. Perhaps these chemical changes alter the way synapses work or cause inflammation that restricts blood flow and inhibits delivery of oxygen to the brain, she said.

Dhurjati’s map may change and grow as the research proceeds. For now, it provides a scaffolding to inform that research and help put each component into context.

At this point, it is unclear how this research might translate into treatments in the future.

Introducing beneficial microbes known as probiotics to the system through diet, supplements, or injection could yield some benefits.

“However, the gut community is very strong and has its own immigration and customs department. So while probiotics theoretically could be a potential way of treating this, I don’t know how easy it is,” Dhurjati said.

For families living with the symptoms of autism everyday, that potential, however small, is a spark of hope.

In Delaware alone, more than 1,200 children have an educational accommodation for autism. That does not count children who have very mild symptoms, are homeschooled, or attend specialized private schooling for severely autistic children.

Parents of children with autism go to extraordinary lengths to learn about the effects of autism and potential courses of treatment, said Teresa Avery, executive director of Autism Delaware, a non-profit advocacy organization headquartered in Newark.

“Diet changes are something that have been talked about in the autism community for quite a while,” Avery said. Many parents have tried omitting gluten, buying organic, or going vegan.

There are over-the-counter products that provide probiotics, including fortified yogurt, and chewable supplements. These contain very specific strains of probiotics that have not been studied in conjunction with autism, Herbert cautioned. She added that even if a probiotic were identified as being effective in mitigating symptoms, it would not likely be a silver bullet.

“Unfortunately, there’s no one thing that’s going to fix anybody’s kid. For the most part, it’s going to take a whole lot more work than that,” Herbert said.