Research & Education

Gut Feelings: Microbiota Modulation of Neurotransmitters

A growing amount of research is identifying various pathways of communication (or “crosstalk”) along the “gut-brain-axis” including the immune system, enteric and autonomic nervous systems, and neuroendocrine system, and is pointing to clear links between the gut microbiome (which contains some 100 trillion microorganisms) and mental health. It is well-established that our second brain (aka the enteric nervous system) influences our stress response, anxiety and depressive-like behaviors, and also plays a critical role in the development of diseases and disorders of the enteric and central nervous systems.


Microbial Composition and Personality Traits

It is well-established in research that an altered blood-brain barrier (“leaky brain”) and impaired intestinal barrier function (or “leaky gut”) both play a role in neuroinflammation. Other problems in the gut, including altered microbial composition or intestinal dysbiosis, also contribute greatly to neurological and psychological health. A recent cross-sectional study published in March in the Human Microbiome Journal discovered that the same microbial strains within the gut microbiome that are associated with extreme behavioral traits in autism spectrum disorder may also influence the social behavior of the general population to a milder degree. Interestingly, researchers found that people who were more sociable and had larger social networks had a more diverse intestinal microbiome. On the other hand, people with higher anxiety and stress had reduced microbial diversity in their gut. This study was the first to relate human microbiome diversity with sociability and personality traits.


Microbial Endocrinology

The microbiota within the gut has been shown to produce and modulate a range of host neurotransmitters, including serotonin, dopamine, epinephrine, norepinephrine, acetylcholine, histamine, and gamma-aminobutyric acid (GABA). “Gut dysbiosis might lead to imbalances in neurotransmitters, inflammation, or heightened activity of the HPA axis that regulates the stress response.” Cell culture studies show that an abundance of gut bacteria from the Bacteroides genus produces GABA, and that “the relative abundance of Bacteroides is negatively associated with signatures of depression, suggesting that bacterially derived GABA may play a role in the microbiome-gut-brain axis.” In the GI tract, serotonin (5-HT) is made by enterochromaffin cells (a specialized endocrine cell), mucosal mast cells and myenteric neurons. Though the molecular mechanism is unclear, gut microbes regulate host peripheral 5-HT levels in the colon and blood, and spore-forming bacteria modulate the metabolites that promote colon 5-HT biosynthesis, suggesting that altering the microbiota couple improve serotonin-related disease symptoms. 


Probiotics and Depression

Considering major depressive disorder (MDD) is the leading cause of disability worldwide, and the advances in research regarding this bidirectional communication between the brain and the GI system linking psychiatric disorders (such as MDD) to changes in the gut microbiome, alternative treatment options from conventional pharmacology are needed to combat this disorder. In addition to increasing production of GABA, probiotics have been shown to have antioxidant abilities and improve nutrient absorption, all implicated in depression pathophysiology. Results from a systematic review published in Annals of General Psychiatry provide compelling evidence that probiotics alleviate depressive symptoms, noting “that it is likely that daily consumption of a probiotic supplement could have a positive effect in improving mood, anxiety, and cognitive symptoms present in MDD.”


Diet and Supplements to Help Restore Balance

This intimate relationship and communication between our gut and brain further bring into focus the importance of maintaining an optimally functional GI tract. This also strengthens the view that perhaps assessing gut health be made a priority when evaluating new and established patients. 

Patients who suffer from mood disorders such as depression and anxiety, and/or those who have neurocognitive issues, need to address the underlying cause, which may very well be rooted in the gut.

It is well-known that a gluten-free, casein-free diet (along with other major allergenic foods) be implemented in the case of inflammatory conditions, including both neurological and gastrointestinal inflammation. Other common dietary measures may be beneficial such as following a specific carbohydrate diet, GAPs diet, and a low FODMAP diet to help reduce inflammation and help rebalance gut bacteria. Because gut microbes can alter the levels of neurotransmitter-related metabolites affecting gut-to-brain communication, thus altering brain function, probiotic supplements may help decrease depressive behaviors and enhance mood (as mentioned above). Probiotic therapy may also be a target for optimizing vagal nerve activity, and hence, helping to improve depression, anxiety, and other common psychiatric conditions.

The link between serotonin production and function with vitamin D and omega-3 fatty acid levels suggests that these nutrients may support brain function and affect our behavior. Supplemental magnesium L-threonate is also an effective micronutrient for supporting mental health, cognitive function and reducing overall anxiety and stress. Nutrients and herbs designed to promote the activity of calming neurotransmitter production and normal stress response such as 5-HTP, GABA, glycine, chamomile, saffron and sceletium extracts, inositol, and L-theanine, along with several members of the B vitamin family to support neurotransmitter synthesis, may also be helpful for supporting a healthy mood.