Reader, with Daylight Savings Time behind us, and long winter nights ahead, what better time is there to talk about the one activity that unites us all? No, I’m not talking about readying ourselves for the holidays—I’m talking about cozying up with a blanket and a good book! Admittedly, when perusing the bookstore shelves, I tend to gravitate towards nonfiction and literary fiction—but I have a soft spot in my heart (and my soul) for books about the mysteries of the universe, including the greatest mysteries of all—the origins of consciousness and of life itself. In these books, where a deep scientific mystery must be solved, they tell the stories of brilliant scientists who, “standing on the shoulders of giants,” pull the pieces of the puzzle together in a way that creates awe and wonder. Perhaps I gravitate toward these mysteries because of the problem-solving nature my work: when I see a new patient who is suffering, the underlying causes of their emotional pain is a mystery I seek to solve. Every mystery can be solved with finding the right set of clues—and the difference between a great “detective” and a bumbling one often lies in knowing where to look. When it comes to the mystery of mental illness, it was often thought those clues were predominantly found in the brain. In reality, mental illness is a genetic and epigenetic whole-body experience, and the search for clues should be conducted accordingly. One of the biggest mysteries in the field of psychiatry is Autism Spectrum Disorder—and with pop culture increasingly shining the spotlight on this complicated disorder, the puzzle pieces that comprise it are certainly some of the most controversial. But research now suggests an important clue in solving the puzzle of ASD may be lingering in our gut microbiome, just waiting for a good detective to pay attention. Is it possible to treat ASD by treating the trillions of bacteria in our gut? Let’s walk through this mystery together!

The Great Mystery of Autism Spectrum Disorder—and How One’s Microbiome May Play a Role

We know from prior blogs in this series that depression is a complex disease as it lives in multiple places in the body, including our brain, gut, and immune system. Bipolar disorder is much the same. Like these two mental illnesses and so many more, Autism Spectrum Disorder, or ASD, also lingers throughout our body—but, as the name would suggest, ASD is so vast and varied in terms of its manifestations that there is no one “disorder” but many that fall under this umbrella category. While the developmental disorders that fall under ASD vary in terms of their type and severity of symptoms, they do share a core group of characteristics, including the display of repetitive and restrictive behaviors and difficulty in communication and interaction with people. ASD effects 1 in 59 individuals in America—yet despite its prevalence, the causes of the disease remain poorly understood. Factors that have thus far been associated with ASD range from the genetic to the environmental, from nutritional deficiencies to nutritional overloads, to virus exposures to immune system dysfunction to allergies. To demonstrate the variability in just one of these categories—the genetics of autism—ASD has been associated with more than 100 genes, and roughly 400 genes may be associated with ASD susceptibility. Some of these genetic variations, like CACNA1C, ANK3, BDNF and COMT, are analyzed in Genomind’s Professional PGx Express. To revisit our detective metaphor, you might say the search for a root cause of ASD is like searching for a single clue in a city the size of Manhattan. When mapping your search for answers, it’s hard to even know where to begin!

That’s why the following fact is so significant: In the last few years, more and more research has found a significant connection between the gut microbiome and ASD. A considerable number of patients with ASD also have gastrointestinal dysfunctions, and—here’s the kicker—severity of GI symptoms in individuals with ASD correlate strongly with the severity of their ASD! To me, this amounts to finding a needle in a haystack: determining the link between the gut and ASD could lead to a revolution in our understanding of the disease—and to novel therapeutic approaches. Luckily, researchers have already begun to undertake this work—and they’ve offered some interesting insights.

Leaky Gut—Autistic Crosstalk

Bacterial composition of the microbiome can vary drastically between a healthy patient and a patient with mental illness, with the latter often suffering from a dysbiotic gut in addition to the symptoms of their disease. Because of what we know about the gut-brain axis—namely, that our gut can carry messages up to our brain that can not only impact our mental health but can even epigenetically alter the expression of our genes—we know that an unhealthy microbiome, one in dysbiosis, fails to create the right messenger molecules, thereby conveying disinformation to and dysregulation of the brain and our entire nervous system. Think of this as “toxic crosstalk” between the gut and the brain. We also know that a dysbiotic gut—a Leaky Gut—can lead to more toxins entering our blood stream (such as bacteria, bacterial fragments, and incompletely digested food molecules), triggering a chronic inflammatory response that further impacts our mental health for the worse. Individuals with ASD often exhibit dysbiosis—and their microbiomes frequently share some key characteristics. First, their microbiomes tend to show reduced microbial diversity, which can often lead to the “overgrowth of harmful bacteria contributing to the severity of autistic symptoms”. Second, their microbiomes show higher levels of Lactobacillus, Clostridium, Desulfovibrio, Caloramator, Alistipes, Sarcina, Akkermansia, Sutterellaceae and Enterobacteriaceae.  Third, their microbiomes show decreased levels of Bifidobacterium, a genus of gut bacteria that helps to reduce inflammation; as well as reduced levels of Prevotella, Coprococcus and Veillonellaceae, which are responsible for carbohydrate digestion and fermentation, processes that produce many of those important “crosstalk” molecules like SCFAs—short chain fatty acids—that facilitate communication between gut bugs and human cells, and between the gut bugs themselves . Arguably, this could be understood as “autistic crosstalk” throughout the body.

These are not the only shared traits found in the microbiomes of patients with ASD—but they do suggest the disorder is as much a concern with the gut as it is a concern with the brain’s physiology. If that is the case, what solutions might there be by treating the gut for ASD? Let’s take a look at two possibilities.

Could Probiotics Ease Symptoms of ASD?

A gut in dysbiosis plays a role in poor mental health. Feeding your gut right with prebiotics and sending in healthy gut bugs in the form of probiotics to whip it back into shape have both been shown to ease symptoms of depression and other mental illnesses—and research is in its early stages to determine whether and to what extent this could be a treatment for symptoms of ASD as well. Early evidence shows that by reducing gut inflammation, probiotics do indeed have a positive impact on children with ASD. It also shows that probiotics can “act via the gut-brain axis to influence neurotransmission and mood states”. Because of the diversity of symptoms and causes of ASD, more research must be conducted to determine which probiotics and prebiotics may have therapeutic impacts—but the field is ripe for more hopeful discoveries.

Is “Repoopulating” the Gut—a Fecal Transplant—the Future of ASD Treatment?

If the gut microbiome causes symptoms of ASD, what would happen if the dysbiotic microbiome was entirely replaced with a healthy microbiome? Reader, not only is that a possibility—it could be the future of treatment for ASD and other mental illnesses. Microbiota transfer therapy involves an antibiotic treatment, a bowel cleanse, and a fecal transplant. The process can take weeks, but by the end of treatment, patients have a new “repoopulated” microbiome—and in many cases, that newly healthy microbiome has a huge impact on their mental health outcomes. In a study of microbiota transfer therapy with individuals with ASD, researchers found substantial changes in both gastrointestinal and ASD symptoms by the end of treatment—and the positive changes were sustained weeks after treatment ended. Patients saw an 80% reduction of GI symptoms and a 22% reduction in ASD symptoms as measured by CARS—a system that rates core symptoms of the disorder. As with probiotics and prebiotics and ASD, more studies must be conducted, but microbiota transfer therapies could be the next revolution in precision medicine—as consequential as genetic testing in helping patients become whole and healthy, both physically and mentally.

Reader, I’m no giant in the field of unlocking the mysteries of the universe, but I do love to solve mysteries of human health and wellbeing—and these promising new fields of research around Autism Spectrum Disorder only further my suspicions that evaluating and treating the microbiome might be the missing link for many mental health struggles—and treatment of those gut bugs could offer healing potential for millions of patients who are suffering. We’re homing in on the root of the mystery of ASD—and I can’t wait to see it solved!

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*Although lessons learned from the treatment of actual patients are included in the patient stories on this website and blogsite, the historical events and facts represented have been changed to protect the identities of any real patients and to protect their confidentiality. For example, the names, ages, careers, the number and sex of their children, as well as the careers of the patients’ parents have been deliberately altered, as well as other alterations that have been made. Consequently, all characters appearing on these sites are fictitious. Any resemblance to real persons, living or dead, is purely coincidental.

**Author’s financial disclosure: Genomind and Potomac Psychiatry have an ongoing marketing collaboration aimed at raising visibility for Genomind pharmacogenomics services and Potomac Psychiatry’s Genetic Testing Consultations. Dr. Kehr holds no ownership interest in Genomind and receives no consulting fees.

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