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The Connection Between Autism Spectrum Disorder and The Gut Microbiota



Gastrointestinal (GI) dysfunction and symptoms are commonly reported among children with Autism Spectrum Disorders (ASD). Forty seven percent of children with ASD have GI issues and are nearly four times more likely to have frequent, recurring GI issues when compared with those without. (1, 2) Symptoms often include chronic constipation, diarrhea, abdominal pain, gastroesophageal reflux (GERD) and/or vomiting. (1)


These GI symptoms are frequently associated with a disruption in the GI microbiome, or dysbiosis. Simply put, dysbiosis is when there are more “harmful” bacteria than “healthy” bacteria living in your intestines. There are well established links between disruptions in the microbiome and a number of mental disorders including depression, anxiety, mood, cognition, and neurodevelopmental disorders, such as ASD. (3)


Dysbiosis can cause inflammation in the intestines and can damage the cells lining the GI tract. If these cells are damaged, they are unable to protect the rest of the body, including the brain, from potentially harmful molecules or microbes.

The Gut-Brain Axis

Research has proven that the gut microbiome is connected to the central nervous system in a bidirectional communication pathway called the gut-brain axis. This acts like a telephone line between the GI tract and brain. This line is heavily influenced by the health of the cells that line the GI tract and gut neurotransmitter levels. Bacteria have been shown to consume and produce a wide range of neurotransmitters, such as dopamine, norepinephrine, serotonin, or gamma-aminobutyric acid (GABA). (4)


The health of gut cells highly depends on the types and the amounts of bacteria living in the gut. Imbalance between “healthy bacteria” and “harmful bacteria” can trigger an immune response and inflammation. Inflammation is known to damage the cells lining the GI tract. Damage to GI cells can interfere with neurotransmission and the gut-brain axis which can eventually impact brain function and behavior. (2,3)

Dysbiosis

More about dysbiosis. Although the bacteria in the gut, or microbiota, are involved in the absorption, metabolism and storage of nutrients, the primary role of microbiota is to digest nutrients from foods that are indigestible (5) Different types of bacteria are responsible for digesting specific nutrients.


Due to these specific bacteria-nutrient relationships, the number of and types of gut microbiota differ based on diet patterns. For example, diets rich in prebiotics that are high in fiber, and low in simple carbohydrates (sugars) promote the growth of healthy bacteria. Diets that are high in simple sugars and low in fiber can lead to bacterial overgrowth.


Leaky-Gut (Intestinal Permeability)

As gut bacteria digest nutrients, they release break-down products called metabolites. Harmful bacteria release metabolites such as enzymes and endotoxins that damage the cells lining the intestinal wall. When excess bacteria, their metabolites or damaged GI cells are detected by the immune system, an immune response is activated. This causes more immune cells to be sent to the intestines to help fight the bacteria and repair the damaged GI cells.

This immune response eventually causes inflammation which can actually cause more damage to the cells that line the intestinal wall. Normally, these cells are tightly packed like soldiers standing shoulder-to-shoulder protecting our blood and body from any harmful bacteria, toxins or other molecules in the gut.


As the gut becomes inflamed, little channels between these cells start to open up. Bacteria, toxins, and other molecules from the gut can “leak” through these channels into circulation. A term that is often associated with leaky-gut is “intestinal permeability”. Increased intestinal permeability simply means there are more channels for molecules to leak through from the gut into circulation.


The bacteria, toxins, and other molecules that leak out of the GI tract travel through the lymphatic system and the blood to other organs. When these molecules are detected throughout the body, immune responses are constantly triggered which can lead to systemic inflammation. Not only does this disrupt a number of bodily functions, but it is especially dangerous for the brain. If these harmful molecules reach the brain, another localized inflammatory response is triggered. Brain cells are very sensitive to inflammation and are easily damaged. This damage causes cell dysfunction and thereby disturbances in behavior and cognition.


The Connection To Autism

Despite the prevalence of ASD, the cause and reliable treatments are still not well understood. Early behavioral and educational interventions have shown to be effective for treating some autistic symptoms, but there are still very limited medical therapies, medications and supplements that target the core of ASD. (1) Studies suggest the gut plays an important role in the development of ASD and its related symptoms. (6)

Several studies have found that individuals with ASD have altered levels of harmful bacteria, metabolites and proteins. There is strong evidence that there are higher levels of harmful bacteria, such as Clostridium and Bacteroidetes, in children with ASD when compared to those without. (7) Some of these bacteria release toxins that cause inflammation in the GI tract and may lead to systemic inflammation.


Low levels of Bifidobacterium have been found in the gut microbiome of children with ASD. (7) Bifidobacterium produces a molecule named GABA. Low levels of GABA are associated with low levels of glutamate. Low glutamate levels are associated with autistic symptoms such as the severity of anxiety and social behavior. (8)


Another area of research focuses on short chain fatty acids (SCFAs) such as propionic acid. (7) SCFAs are produced by bacteria fermenting fiber in the gut and are important immune system regulators in the GI tract. Abnormal levels of SCFAs in the gut can cause an inflammatory response. As a reminder, inflammation in the gut can cause spaces between the cells that line the GI tract; these spaces allow molecules to escape into the blood and eventually the brain. Propionic acid is a SCFA that is produced by some Clostridia species and Bacteroidetes that can escape the GI tract and is highly toxic to brain cells. High levels of propionic acid have been found in children with ASD and may interfere with neurotransmitter production and other regulatory processes throughout the body (7)


In addition to dysbiosis, high levels of zonulin and propionic acid have also been found in children with ASD. (9) Zonulin is a protein that regulates how tightly the cells in the GI tract are packed together. Higher levels of zonulin are associated with more gaps between the cells and allow for harmful molecules, such as the toxins released by Clostridium and Bacteroidetes, to escape the GI tract and to enter circulation.


In some cases, treating the altered gut microbiota results in less severe autistic symptoms. This is a relatively new area of study, so there is limited research, but results suggest probiotic and microbiota transplant therapies may be effective for a number of individuals. (7)

Due to all of these relationships between gut health and brain health, it has been proposed that treating gut abnormalities may lead to improved behavior and autistic symptoms.



Treatment Options

Antibiotics are sometimes used to treat specific microbial overgrowth. However, antibiotics rarely target just harmful bacteria and some treatments can actually cause dysbiosis. (4) Overuse and misuse of antibiotics can lead to antibiotic resistance. When harmful bacteria become resistant to antibiotics, they become even harder to treat. It is important when working with a health practitioner that the child is being monitored.


There is evidence that treatments for dysbiosis and a balance of gut microbiota has potential to treat autism symptoms. (10). The focus here is to regulate the gut-brain axis by supporting the growth of healthy bacteria and starving harmful bacteria. As the levels of healthy/harmful bacteria begin to find a balance, the gut will have a chance to heal.

Treatments and interventions that target the gut microbiota such as diet, prebiotics, probiotics, and fecal microbial transplant (FMT) may be beneficial treatment options for some autistic symptoms (10). Diet and probiotics have resulted in the most successful outcomes and have less side effects than other treatment options. There are also other supplements that help the gut heal faster and support the growth of healthy bacteria.


There are tests that can be done to determine the composition of your gut microbiota and also steps that can be taken to promote the growth of healthy bacteria to achieve a more balanced microbiome. All of these options are discussed with Greer at Biomedical Healing for Kids. Greer is experienced in microbiota analysis and is able to help create a comprehensive, individualized plan of action with you.




Authors

Marguerite Drowica Dietetic Intern

Greer McGuinness MS, RD, CDN, CLT, Dt.Sp.

Founder of

Biomedical Healing For Kids



Sources

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8. Horder J, Petrinovic MM, Mendez MA, Bruns A, Takumi T, Spooren W, Barker GJ, Künnecke B, Murphy DG. Glutamate and GABA in autism spectrum disorder—a translational magnetic resonance spectroscopy study in man and rodent models. Transl Psychiatry [Internet]. 2018 [cited 2020 Oct 20];8. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5970172/

9. Özyurt G, Öztürk Y, Appak YÇ, Arslan FD, Baran M, Karakoyun İ, Tufan AE, Pekcanlar AA. Increased zonulin is associated with hyperactivity and social dysfunctions in children with attention deficit hyperactivity disorder. Comprehensive Psychiatry. 2018;87:138–42.

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