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The Link Between Gut Bacteria, Tryptamines, and Mental Health

It’s long been known (in some cultures at least) that gut bacteria are a critical component in overall health. For example, Traditional Chinese Medicine, which is believed to be able to treat and prevent an overwhelming number of illnesses, is largely centered on balancing the gut microbiome. Although the West is slow to catch up, we’re getting there, and a growing number of healthcare practitioners, nutritionists, and researchers are taking a fresh look at this topic. These days, you can find quite a bit of information on the importance of a stable gut microbiome, even in relation to mental health. What is less frequently discussed, is the connection between bacteria in the gut and tryptamines in the brain, and the importance of this link. So let’s take a closer look.

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The importance of a healthy gut microbiome 

It’s common knowledge that the gut microbiome plays a very pivotal role in overall health by helping control digestion and regulating the immune system, but it wasn’t until fairly recently that the connection between the gut and brain has become a subject of more serious focus. As a matter of fact, the link is so prominent that in recent years, researchers have begun referring to the gut as the “second brain”.  

Roughly 40 trillion bacterial cells, as well as various fungi and viruses, live on and in the human body. These cells are collectively known as the microbiome. The 1,000 or so microbes in the GI tract are referred to as the gut microbiome, and are largely located in the cecum, a small pouch at the end of the large intestine near the colon. 

The gut and brain are connected via the vagus nerve through the gut-brain axis (GBA). Upon digestion of food, enzymes are produced that activate various neurotransmitters and gut hormones. These neurotransmitters and hormones then aid in the regulation of our most important physiological and neurological functions. 

An unhealthy gut is believed to be the root cause of many diseases and disorders including but not limited to obesity, type 2 diabetes, skin conditions like acne, eczema, and psoriasis, autoimmune problems, migraines, irritable bowel syndrome, and heart attack/stroke. Additionally, due to the relationship between the gut and brain – anxiety, depression, and other psychiatric conditions can also be symptoms of an imbalanced gut microbiome. 

Tryptophan and tryptamines

Now, to further expand more on those neurotransmitters I mentioned above. Two of the primary neurotransmitters/hormones that regulate physical and neurological functions in humans are serotonin and melatonin, both of which belong to the tryptamine class of compounds. Serotonin (a neurotransmitter) is a precursor to melatonin (a hormone), and the healthier your levels of serotonin are, the more melatonin your body will produce. Together, serotonin and melatonin are responsible for regulating an array of bodily processes such as mood, sleep, digestion, healing/clotting, appetite and weight, cardiac health and blood flow, bone growth and density, sex drive, and focus. 

On a broader scale, tryptamines (and all derivatives) are indolealkylamine molecules that come from Tryptophan, an essential amino acid found in many plants and animals. In humans, the digestion of dietary proteins in the small intestine leads to the release of tryptophan – we do not produce it on our own. Despite this, tryptophan is vital for normal growth in infants and for the production and maintenance of the body’s proteins, muscles, enzymes, and neurotransmitters. A deficiency can lead to depression, anxiety, irritability, impulsiveness, inability to focus, poor dream recall, insomnia, nausea, motion sickness, seasonal affective disorder, and several other neuropsychological symptoms.

After tryptophan is released during digestion, it is then absorbed by the intestinal epithelium and dispersed into the bloodstream. Once it reaches the brain, tryptophan undergoes a decarboxylation process and becomes a tryptamine compound, which will then present as those aforementioned neurotransmitters and hormones.

In nature, most tryptamines are psychoactive hallucinogens. Some of the better-known ones include N,N-dimethyltryptamine (DMT), psilocybin and psilocin, and ibogaine. 5-MeO-DMT, or toad DMT, is another popular one. Over the last decade or so, a new generation of synthetic tryptamines have emerged. One of more established one is LSD (although this is an ergoline-based tryptamine), but in recent years, drugs like 5-MeO-DiPT, 5-MeO-DPT, AMT, 4-AcO-DMT and 4-AcODiPT DMT have been gaining some notoriety as well.  

Tryptamine compounds act as agonists of the 5-HT2A receptor and are known for creating profound changes in thought processes, temperament, and sensory perception. Tryptamine is a partial agonist of the trace amine-associated receptor, hTAAR1 in humans. Activation of hTAAR1 is believed to be a potential treatment mechanism for various mood and neuropsychiatric disorders, of particular interest is schizophrenia. Research on other hTAAR1 agonists has found that they produce anti-depressant activity, increase cognition, and reduce stress and addictive behaviors. 

What does this all mean? 

There are dozens of different reasons why good gut health is the foundation of our general wellbeing, but the main thing that I want to point out in this article is the connection between tryptophan in the gut and tryptamine in the brain. Although more studies are needed on the significance of this connection in humans, we do know that the gut microbiota produces a huge array of tryptophan metabolites, which become various indolic compounds such as tryptamine.  

The compounds are an integral part of the central nervous system (CNS), as they can signal both locally to the intestinal mucosa, and to distant organs throughout the body, including the brain. Additionally, a growing body of evidence indicates that healthy gut microbiota rich in tryptophan metabolites, may be crucial in shaping the gut-brain axis (GBA). The GBA is a “two-way biochemical signaling that takes place between the gastrointestinal tract and the central nervous system”, or in other words, a direct pathway of communication between the gut and the brain – of which tryptophan and tryptamine are key components.  

Tryptophan is also the sole precursor to serotonin once it converts to a tryptamine compound. One thing to keep in mind, is that we have two different types of serotonin in our bodies: central and peripheral. Central serotonin is the primary neurotransmitter responsible for maintaining homeostasis in the human body – and also plays an important role during CNS development, modulating neuronal differentiation and migration, as well as axonal outgrowth, myelination, and synapse formation. 

Despite its importance, central serotonin only accounts for a very small portion of the body’s total serotonin – about 10 percent. The other roughly 90 percent of serotonin is stored in the GI tract and produced from enterochromaffin cells (ECs). This is referred to as peripheral serotonin, and under standard conditions, it cannot pass through the blood-brain barrier (BBB). Only central serotonin that is synthesized from tryptophan can cross the BBB, meaning that tryptophan-derived serotonin is much more functional than peripheral serotonin. So that speaks to the importance of maintaining a healthy gut on an even higher level.

Positive outcomes in psychedelic therapy  

Drugs alone are almost never the be-all, end-all solution to treating any mental health condition. In addition to proper medication (psychedelics in this case) or talk therapy, supplementation and lifestyle changes are equally important. Because a healthy gut microbiome is so closely related to serotonin levels, it’s logical to assume that a focus on proper diet may lead to better outcomes in psychedelic-assisted therapy, especially because most psychedelic drugs are serotonergic.  

According to a 2014 systematic review titled Pharmacology of Hallucinations: Several Mechanisms for One Single Symptom?, “There are three things that can happen in the brain when we take hallucinogenic drugs: (1) activation of dopamine D2 receptors (D2Rs) with psychostimulants, (2) activation of serotonin 5HT2A receptors (HT2ARs) with psychedelics, and (3) blockage of glutamate NMDA receptors (NMDARs) with dissociative anesthetics.” Let’s focus more on number 2, the serotonin model. 

Even though the study did outline a few other neurological causes for hallucinations, they emphasized how “stimulation of serotonin 5HT2AR on cortical neurons may affect the functioning of the cortico-striato-thalamo-cortical loops and triggers a disruption in the thalamic gating of sensory and cognitive information. It has been proposed that this process triggers a breakdown of cognitive integrity and results in the subsequent occurrence of aberrant feelings and perceptions.” 

Simply put, psychedelics activate our serotonin receptors, so making sure that the cycle of central serotonin production is running smoothly might be fundamental to faster, longer lasting, and more positive results when incorporating these hallucinogenic compounds into mental health treatment plans.  

Final thoughts  

To summarize, the order goes like this: Dietary protein –> tryptophan –> tryptamine –> serotonin –> melatonin. If anything can be gathered from the research I did on this, I would say it’s the importance of eating a healthy, balanced diet. At this point, the connection between gut bacteria and mental health is undeniable, and it seems that tryptamine is a huge element here. So if you want your body to produce more of these compounds, just remember to eat right, stay hydrated, and don’t skip on the protein!

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