The gut microbiome has become one of the most exciting fields of medical inquiry of the last decade. Much of the research began as an effort to understand and address a variety of chronic stomach ailments that have come into popular focus over the last 25 years, conditions such as Crohn’s disease, gastroesophageal reflux disease (GERD), ulcerative colitis, and Irritable Bowel Syndrome (IBS). Psychotherapists and psychologists have long postulated a connection between psychological ailments, psychosocial stressors, and stomach disorders. For example, 61% of people with IBS also have a DSM-diagnosed anxiety disorder. The classic understanding posits that high stress levels and anxious tendencies can cause disturbances in the gastrointestinal tract, including high stomach acid levels and hyper-reactive bowels, that may lead to various GI disorders. 

And while that is true, recent findings regarding the impact of stomach bacteria on the mind and behavior have surprised the scientific community, challenged the classical paradigm, and opened up new lines of inquiry.

The Emergence of Psychobiotics

Professor Ted Dinan of University College Cork in Ireland, one of the pioneers in the field, introduced the term psychobiotics in 2012 to describe the specific bacteria that when consumed result in beneficial effects on mood, motivation, and cognition.  

To understand how infinitesimally small bacteria in the stomach can affect the subjective experience of depression or anxiety, we need to understand a bit about the stomach’s relationship with the brain, a relationship we still don’t fully understand, but that is the focus of increasing research globally.  

The Stomach Has A Brain

To begin with, it is important to note that the stomach has its own “brain:” the enteric nervous system. Often nicknamed “the second brain,” this mesh-like network of 500 million neurons lines our entire digestive tract from the esophagus to the anus. It is responsible for co-ordinating and managing all our digestive functions and it does so with input and feedback from the brain and central nervous system, via the vagus nerve.

The Vagus Nerve

The vagus nerve is a very large bundle of nerves that runs from the brain stem to vital organs including the stomach. Scientists were astounded to discover that 90% of the nerve fibers in the vagus nerve are communicating signals from the gut to the brain in a bottom-up manner. 

That’s right, this major super-highway of nerve fibers is mainly delivering information, signals, and communication from our stomach to our brain. And much of that signaling is being generated by the gut bacteria through its constant dialogue with the second brain.

The vagus nerves terminates in the brain stem but has direct neural links to a variety of brain regions that are associated with processing and regulating mood, emotions, stress, and hunger. And it is these pathways that researchers think is fundamental to how the gastrointestinal microbiome can impact, and potentially cause, anxiety and depression. 

In fact, one novel therapy for treatment-resistant depression involves the ongoing electrical stimulation of the vagus nerve via a pacemaker-like implanted device.

The Gut Brain Axis

This bi-directional relationship between the brain and the GI system is called the “Gut-Brain Axis” and the star player in this relationship between the gut and the brain is our gastro-intestinal microbiome. This is the multi-billion strong community of microorganisms (bacteria, protozoa, and viruses) living in our gut that digest our food, synthesize important vitamins, and help mount immune responses to harmful pathogens we have consumed. The average human has between 3–6 pounds worth of these microorganisms in their GI tract and the evidence suggests that they evolved symbiotically with our body’s cells to provide vital functions that our cells can not. It's hard to underestimate the importance of these billions of bacteria living in our colon. Beyond their critical role in digestion they are intimately involved with our immune system, endocrine stress response system, and our central nervous system.

Making An Anxious Mouse Confident

One of the pioneering studies proving that stomach bacteria could affect behavioral responses was conducted in 2011 by Premysl Bersick at McMaster University. Bersick and his team experimented with fecal transplants (exactly what it sounds like) between mice that were genetically bred to be timid and anxious and mice genetically bred to be bold and exploratory.

Bersick showed that when the timid mice received fecal transplants from bold mice, they become less anxious and more exploratory. The reverse also held true: genetically bold mice were much more cautious and fearful after the introduction of stomach bacteria from anxious mice. Later research indicated that obese mice lost weight after receiving fecal transplants from thin mice, which has led to a novel new approach for treating obesity. 

Since then, dozens of studies on mice have been conducted pinpointing the effects of specific gut bacteria on mouse behavior and neurochemistry. Mice are used due to ease of experimental study and because the primary means of isolating the effects of one strain of bacteria is by using animals that have been bred, raised, and kept in a germ-free environment. Novel stomach bacteria are introduced one a time to see the effects on the mice’s behaviors and neurochemistry and the results have been truly incredible. 

The Tryptophan-Serotonin Connection

Tryptophan is an essential amino acid that we must get from food and a critical precursor for the synthesis of Serotonin. Tryptophan crosses the blood brain barrier and how much gets there is regulated by our gut microbiome. One animal study showed that the stomach microbe Bifidobacteria infantis was shown to significantly increase blood plasma tryptophan levels. The brain stores very little tryptophan and therefore needs fresh supplies daily to create Serotonin which is critical in mood regulation. It turns out that our gut bacteria have a powerful regulating effect on tryptophan levels and how much tryptophan reaches the brain.

The Role of GABA

A a 2011 study showed that genetically anxious mice fed broth with Lactobacillus rhamnosus were more exploratory and risk-taking and were less likely to give-up in a forced swim tests than the control mice. The mice fed L. rhamnosus also showed less cortisol secretion in response to stressors as well as an increase in the number of receptors for the neurotransmitter GABA. GABA is the principal inhibitory neurotransmitter and it tamps down neural activity throughout the central nervous system. It is also the target site for the anti-anxiety medication such as Xanax. When the vagus nerve of mice in this study were severed, the effect disappeared, making it clear that the the bacteria were acting through the vagus nerve to alter brain levels of GABA.

Specific strains of beneficial gut bacteria have also been shown to actually secrete GABA and recent unpublished research shows that consuming specific psychobiotics increases GABA levels in the brain, so we know that GABA is one of the neurotransmitters acted upon by the gut microbiome.

An Endogenous AntiDepressant

In the process of breaking down indigestible nutrients such as fiber, our gut flora produce short chain fatty acids that have various metabolic effects. One of these, butyrate, has been documented in several studies to have antidepressant properties. Butyrate has the ability to cross the blood brain barrier and effect central nervous system neurochemistry, including raising levels of Serotonin in the brain. And it is a key product of our intestinal microbiome because it is also used as food by the cells lining the colon.

Mediating Our Stress Hormones

Several strains of Bifidobacterium and Lactobacillus bacteria have been shown to decrease cortisol and norepinephrine levels and result in reduced anxious behaviors in animal studies and reduced self-reported anxiety in human studies. The research suggests that benefecial stomach bacteria can temper the Hypothalmus-Pituitary-Adrenal Axis that is the primary mechanism of the fight-or-flight stress response system.

Stress hormones also inhibit the immune system, which is why chronic stress creates susceptibility to infection and illness leading to chronic low-grade inflammation. This is a marker commonly seen with depressed patients.

Human Trials

While there are is a ton of experimental research on mice and a growing base of exploratory studies on humans, there is a substantial gap between the animal research findings and the clinical data on humans. We just haven’t seen the kind of rigorous randomized double-blind placebo-controlled clinical studies evaluating the effects of psychobiotics on human subjects with mental health diagnosis.

To date, there has been one study of this kind, conducted in Iran in 2016 and it indeed found significant decreases in depressive symptoms versus the control group for subjects with Major Depressive Disorder that were administered Lactobacillus acidophilus, Lactobacillus casei and Bifidobacterium bifidum for 8 weeks.

Furthermore, three recent meta-studies that examined all of the human research in the field up to now all came to the same conclusion: probiotics can lead to reductions in symptoms of depression and anxiety, improve mood and reduce stress response in humans with or without depressive or anxiety disorders.

Which Psychobiotics?

While we are still in the early stages in our understanding of psychobiotics, there are a few strains of bacteria that have demonstrated beneficial effects on mood and anxiety in both animal studies and preliminary human studies. And the good news is many of these are found in yogurt and other fermented foods. These include:

Bifidobacteria Species: B. longum, B. bifidum, B. breve, B. infantis, B. bulgaricus

Lactobacillus Species: L. helveticus, L. rhamnosus, L. plantarum, L. reuteri, L. casei, L. bulgaricus, and L. acidophilus

But before you go out and start shopping for the latest in psychobiotic supplements, keep in mind that:

• Psychobiotics need to be ingested alive and in enough quantity to survive the tortuous voyage to your lower intestines and colon. We’re talking 10–100 billion Colony Forming Units (CFUs) required.
• Psychobiotics have synergistic effects when consumed together. Therefore, it is better to consume a cocktail of known psychobiotics together versus individually.

• These bacteria take time to build-up colonies in your GI tract. This means that, similar to antidepressants, you need to consume them for a few weeks before knowing if they will have a psychological benefit. The average administration period used in human studies is around 4 weeks.
• Also similar to antidepressants, you need to keep taking them as many can’t naturally survive long-term in the gut. In various studies the beneficial effects of probiotic supplementation stopped within days once the consumption of them ceased.

The Importance of Nutrition and Prebiotics

There is actually a whole lot more you can do for your gut health than consuming psychobiotics and without these other steps, it's questionable whether psychobiotics can deliver on their potential in the first place. The message from the research is that the health and balance of your intestinal microbiome are hugely important and psychobiotics are just one tool of many. 

Frankly, dietary and lifestyle changes will have a bigger impact than psychobiotics at this pont. Here are a few guidelines that many of the researchers in the field follow themselves:

• Eat Yogurt — This is the original probiotic. Make sure it has live bacteria added after pasteurization. Most “live” yogurt contains psychobiotics bacterial strains.
• Eat a variety of fermented foods such as kimchi, sauerkraut and kefir. These also naturally contain many of the psychobiotics listed above.
• Try to avoid antibiotics unless absolutely necessary. They kill off huge amounts of healthy gut bacteria.
• Eat a great diversity of high fiber plant-based foods (eg fruits and veggies). Different bacteria eat different types of fibers so just taking a fiber supplement will not increase the diversity of your gut biome, which is the key to gut health.
• Limit processed foods as much as possible. They get absorbed swiftly in the upper GI tract and stomach and starve the lower GI tract and intestines, where most of the gut microbiome resides. High-fat/low-fiber diets are known to reduce intestinal microbial diversity
• Consider the Mediterranean diet which in addition to supporting a healthy gut biome is shown to be antidepressant in nature

Gut Ecosystem Management

The general ethos for cultivating a healthy gut microbiome is to think of it as a rainforest or other complex ecosystem. The more diverse the ecosystem, the more resilient it is when exposed to pathogens. Furthermore, the more diverse your gut biome is the less likelihood of one microorganism wielding excessive influence resulting in unhealthy microbial imbalances. The best way to increase the diversity of your stomach microbiome is to eat a variety of different kinds of fiber-rich and naturally probiotic foods. Diversity of diet truly is the key to stomach health and potentially to mental and emotional health as well.