The Gut Microbiota-Neurobehavior Connection (Part 1)

By Lindsay Christensen

Nutritionist @ The Pratt Clinics


Neurobehavioral and mental health disorders, including autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), depression, and anxiety are on the rise. At present, a shocking 1 in 59 U.S. children has autism, compared to 1 in 150 in 2000! 11 percent of U.S. school-aged children have ADHD, and an estimated 6.7 percent and 18.1 percent of American adults suffer from major depressive disorder and anxiety, respectively. What is to blame for soaring rates of neurobehavioral and mental illness? Emerging research points to the gut microbiota as a central factor in the development and pathogenesis of autism, ADHD, depression, and anxiety. However, by beneficially altering the gut microbiota, it is possible to change the course of these disorders, eliminate symptoms, and significantly improve quality of life!

The gut-brain axis

Have you ever been nervous about an upcoming event in your life, such as an exam or public speaking engagement, and felt “butterflies” in your stomach? This strange feeling is a simple but perfect example of the communication that occurs between your brain and gut via a structure called the “gut-brain axis.” 

The gut-brain axis is a bi-directional communication network between your central nervous system (CNS), which includes your brain and spinal cord, and the enteric nervous system (ENS) of your digestive tract. The gut microbiota, the community of microbes inhabiting the intestine, lives in close contact with the ENS. Gut microbes interact with intestinal cells to influence the release of hormones, neurotransmitters, and immune system molecules. These gut-derived molecules interact with the ENS, and, via the gut-brain axis, influence brain function. A healthy gut, with a balanced population of microbes, is thus a prerequisite for a healthy brain! When the gut microbiota is compromised by factors such as antibiotics and an unhealthy diet, the molecular signals sent from gut microbes and intestinal cells to the ENS and CNS changes, ultimately impairing brain function. Via the gut-brain axis, adverse changes in the gut microbiota contribute to changes in the brain and thus to neurobehavioral and mental health disorders. 

A healthy gut and brain begin in infancy

The development of a healthy gut-brain axis begins at birth. A mounting body of evidence indicates that the mode of delivery by which an infant is born significantly influences the development of the gut-brain axis. Infants born vaginally are first exposed to their mother’s vaginal microbiome, whereas infants born via C-section are first exposed to their mother’s skin microbiota and other microbes floating around the hospital. Research indicates that infants delivered vaginally have higher amounts of beneficial bacteria in their guts, which may shape a healthy gut-brain axis. Infants born via C-section, on the other hand, experience delayed bacterial colonization of their intestines, abnormalities in their gut microbiota, and an increased risk of autism and ADHD. 

The method by which a baby is fed also influences gut-brain axis development. Breastfeeding inoculates the infant gut with beneficial bacteria, such as Bifidobacteria, which produce GABA, a calming neurotransmitter. Breastmilk also contains indigestible sugars that fuel the growth of beneficial gut bacteria and stimulates the production of IgA, a molecule that shapes the immune system, in the infant gut. The beneficial effects of breastmilk on the gut microbiota may explain why breastfeeding is associated with positive neurodevelopmental outcomes, including increased resilience to stress during childhood and reduced risks of ADHD and autism. Infants fed formula, on the other hand, have higher levels of Clostridium difficile, an opportunistic bacteria that can become pathogenic if the gut lacks sufficient good bacteria. The dysbiosis induced by formula feeding may impair normal gut-brain axis development. (13) 

Antibiotics also have a huge influence on the gut-brain axis. Children treated with antibiotics during the first three years of their lives have gut microbiotas that are significantly less diverse than those of children who didn’t take antibiotics. Children on the autism spectrum typically have a history of significantly more antibiotic use than neurodevelopmentally normal children. 

How the gut microbiota affects neurobehavior 

How do gut microbes affect neurobehaviors, such as those displayed by individuals with autism, ADHD, depression, and anxiety? The answer has to do with gut microbiota metabolites. As I mentioned before, gut bacteria produce unique molecules as part of their metabolism, including ones similar to neurotransmitters. They also stimulate intestinal cells to produce hormones, neurotransmitters, and immune molecules. The release of metabolites triggered by gut bacteria sends signals to the enteric nervous system and brain via the gut-brain axis. These signals modulate brain function and behavior. 

An overgrowth of pathogenic bacteria and a lack of beneficial bacteria in the gut results in the transmission of skewed signals to the brain. These skewed signals may result in abnormal behaviors, an inability to focus, an impaired stress response, and depressed CNS function. 

Researchers have found relationships between certain neurobehavioral and mental health disorders and bacterial imbalances in the gut. Autistic children frequently demonstrate reduced levels of Prevotella, a beneficial bacterium associated with plant-rich diets, increased Clostridia and Candida, and decreased levels of helpful Bifidobacteria and Firmicutes. Clostridia overgrowth produces neurotoxins that negatively impact neurochemistry, including a compound called 4-cresol that interferes with the conversion of dopamine to norepinephrine, a neurotransmitter required for attention and focus. In fact, 4-cresol has been proposed as a diagnostic marker for autism. High levels of Candida prevent the absorption of carbohydrates and minerals in the gastrointestinal tract and cause a buildup of toxins that harm the brain, including ammonia and propionate.

Children with ADHD also exhibit gut microbiota abnormalities. A slight increase in Bifidobacteria has been observed that may alter the activity of an enzyme involved in dopamine synthesis. Altered dopamine activity decreases something called the “reward anticipation pathway,” a neurological pathway that regulates motivation and the initiation of effort. Interestingly, children with ADHD also have high rates of gastrointestinal issues compared to “normal” children, suggesting that gut dysfunction plays an important role in their behavior.

Anxiety and depression are both stimulated by endotoxins, which are toxins produced by pathogenic bacteria in the gut. In both human and animal studies, endotoxin induces anxious and repetitive behaviors, dysregulates the body’s stress response system, and promotes depression.

In Part 2 of this two-part blog series, I’ll discuss two tests that are useful for diagnosing gut dysbiosis and how you can correct gut dysbiosis and improve brain function with probiotics, prebiotics, botanicals, and dietary changes.

If you need more information or help with your overall health, contact us at The Pratt Clinics.

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