Psychobiotics, The Future of Mental Health?

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.  

A new book co-written by Professor Dinan just came out

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.

Combinations of probiotics shown to work well together

• 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. 

Why You Need A Media Cleanse

Many people I know are freaked out on a regular basis these days. And can you blame them? We’ve got Climate Change, Trump Tweets, North Korea, ISIS, Brexit, mass shootings, sex scandals, hurricanes, fires, and earthquakes… oh my! Its almost as if the entire world is completely falling apart! Except it most certainly is not. While all of these things are real, marinating in the juices of all the world’s “problems” isn’t helpful or functional. In fact, it’s quite the contrary. Since there is nothing any particular individual can do to solve them, being bombarded with these issues 24 hours a day isn’t functional. In fact, it’s a great way to develop what behavioral psychology refers to as “learned helplessness,”a known pathway for depression and anxiety. Is it no wonder that 17% of American adults are taking a prescription psychiatric medication? And let’s not forget that 20% of Americans are taking some kind of prescription opiate painkiller. Excluding the overlap between those two groups, you have nearly 40% of the population taking some kind of prescription medication for pain, unhappiness, or stress.

Ok so there’s a lot of problems in the world and we’re all depressed about them. Well, yes, but that’s not the real story. After all, you can pick any point in human history and find a war, an atrocity, or a natural disaster happening somewhere. Pick any time and any continent and I can pretty much guarantee there was some group of humans fighting with another group of humans in a not very nice way as well as a natural disaster befalling some tribe or civilization somewhere. My point is, this is nothing new. What is new is that we are now constantly notified about and attuned to every disaster and calamity occurring around the world practically 24 hours a day. Obviously the internet and our smartphojnes are part of the problem, but frankly, I think that’s an easy scape-goat for a much more systemic dynamic.

Because there are both political and economic reasons for this as well. And the big one is, you guessed it, money. Our modern American economy is fundamentally based on consumption. 70% of our GDP is made up of consumer expenditures on products or services. So the system we have in place, and its large actors, depend heavily on our consumption for its survival. Consumerism is the core of the American economy engine. And that engine needs constantly increasing fuel. If we as consumers fail to grow our consumption year over year by at least 1%, the economy literally falls into a recession. So there is a lot riding on keeping us consuming.

Remember when smoking was glamorous and sexy?

Several decades ago, before we became a consumer-dominated economy, the burgeoning public relations-advertising-media industry realized that you could prime this consumption by identifying archetypal human needs and positioning consumer products as solutions to these needs. Edward Bernays is widely considered to be the father of this kind of psychological manipulation due to his famous 1929 “Torches of Freedom” campaign that successfully turned smoking cigarettes into a glamorous statement of feminine power and independence. Much of the understanding that underpinned these kind of psychologically manipulative strategies was based in Freudian psychoanalytic theory. Advertisers began consulting with psychologists and psychiatrists to help peer inside the mind of consumers. They didn’t do this because they were curious, they did it because it helped them to get consumers to buy more of their products. And they’ve been doing this ever since.

Over time the marketing industrial complex has refined and developed these methods, using the latest psychological research tools to position every conceivable product and service in a way that stimulates some of our core human drives and pushes us to make that purchase. More recently they’ve been using neuroscience research and methodologies to improve advertising outcomes. This has actually become a thing. Its called “neuromarketing” and its currently very hot in advertising. The point is that these are very sophisticated operators spending literally $10s of billions of dollars a yearwith the sole intent of getting you to buy more stuff.

And the primary way they do that is buy stimulating the drives of comfort, and safety, on one hand, and stimulation, excitement and glamor (e.g. sex) on the other. In one form or another, they are essentially offering to solve the twin existential dilemmas of human existence, fear and boredom. One could easily say, borrowing from the street drug vocabulary, advertisers are selling both “uppers” and “downers”. And they are doing this by anchoring a product or service to one of the aforementioned human drives.

Our traditional media industry, television, cable TV, radio and print media, operate off these principles as well. Their main job is to sell advertising using content that will attract people and get their attention. It didn’t take long for the media industry to realize that scandal and fear-mongering are excellent ways to attract attention, beginning with the Yellow Journalism of William Hearst. So years before the invetion of the news ticker at the bottom of the TV screen, the news was skewed towards negativity and fear-mongering. Obviously our media landscape is much more complex nowadays, but you can see how pretty much every newspaper, TV/Cable channel or digital media property reallies heavily on news that is controversial or stimulates fear, anger, and outrage, or excites and titlitates us with sex, drama, and gossip.

But wait, it gets better! Now we have Google, Facebook, Twitter and Social Media. 90% of their business revenues come from selling these very advertisements. Ignore their platitudes and mission statements about “Doing No Evil” and “Connecting the World.” They are media businesses whose primary role is to sell advertising. To do so, they use every trick at their disposal to get you to be glued to your phone looking at their advertisements. Why is it that “trending” topics are often salacious and outrageous? They may seem to be crowd-chosen, which in one sense they are, but behind the scenes they are carefully cultivated click-bait, designed, enabled, and promoted to get you to keep consuming more advertisements. And they’ve gotten really really good at this. The tricks have filtered down from corporate entities to every day bloggers, and social media content creators. These buttons are being pushed all the time. I mean just look at the title I chose for this article! Designed to grab your attention!

The End-Goal of All Advertising Is Purchasing

So many people I know tell me they don’t have a TV or don’t watch TV but they carry around a personalized advertising delivery device everywhere they go. The push-based notification system on these devices make them powerful attention magnets. People walk around being bombarded by content that is designed to get them to consume more content (and therefore advertisements) or create more content (and therefore advertisements) with the end goal of getting consumers to purchase what is advertised. After all, the end-goal of all advertising is purchasing. If Google or Facebook can’t actually deliver purchases and consumption, then they fail at their job and their business fails. So in a way, these websites are in the consumption-promotion business. And they are very good at it.

The Hedonic Treadmill On Steroids

The Hedonic Treadmill is a philosophical concept that describes how seeking pleasures and comforts is a self-reinforcing feedback loop because once the pleasure is experienced, it dissipates, and we quickly return to our previous baseline state. With advertising, you can stimulate this pleasure seeking again and again because it will never lead to long-term satisfaction. It is the perfect consumption-generation system.

“A true saying it is, Desire hath no rest, is infinite in itself, endless, and as one calls it, a perpetual rack, or horse-mill.” Robert Burton, 1621

And Robert Burton didn’t have access to super models, pornagraphy, designer opiates, Facebook “Likes”, and 1,200 calorie slices of cheesecake. Companies have crearted incredibly concentrated and pleasurable versions of what naturally activate the pleasure/reward feelings in moderate amounts (eg food, sex, social approval) and at these highly concentrated versions are very hard to ignore. And in some ways they are addictive, which makes them the perfect products.

So advertising’s goal is to keep consumers on the treadmill and that consumption of goods/services they are promoting become the object of this seeking. They do this by promising pleasure, comfort, and happines by linking their products to those feeling states, or absence of those products to absence of those feeling states. They also do this by inventing and promoting products that are insanely pleasurable or palatable.

But this is only half the equation. Yes we are wired for hedonism but you can prime the pump of that treadmill a lot more by chronically triggering our stress response system (e.g. the Hypothalamus-Pituitary-Adrenal axis.). How is this done? Well if an animal is kept in a chronic state of stress, it is well documented that it will seek out food, drugs, and other comforts in laboratory settings. The same thing happens to people. As the news, media and political system promote crisis and fear as a means to capture attention and shape a compelling self-serving narrative, we get bombarded with fear and stress-inducing messages. This is a very very powerful neurochemical recipe that makes us more likely to crave and consume what is advertised to us. If you find yourself battling cravings for anything, check your stress levels first.

The Neurochemical Seesaw

I’m not saying this is some kind of co-ordinated conspiracy, but regardless of the reasons, the net effect is a neuro-chemical seesaw in which we bounce between anxiety/stress/crisis and avoidance/distraction/numbing with empty pleasures. Neurochemistry-wise, the news and media primes the Hipothalmic-Pituitary-Adrenal axis with cortisol-releasing messages and consumer advertisements promise us relief with dopamine and endorphin-releasing experiences if we simply purchase the new mattress, gadget, latest superfood, etc.

In many ways our neurochemistry is a map of and reflects the world around us. Our disturbed neurochemistry (eg chronic depression, anxiety, and addiction) makes a lot of sense when you see how dysfunctional our media and economic landscape is…and I’m not even touching on our political environment or spiritual state.

So I’ve laid out why things feel so shitty right now. Now here is where I sell you my product or service to solve just that problem! Just kidding, here is where I outline things that you can do to get out of this cycle that don’t involve a monetary transaction. I propose that tuning this stuff out will help restore sanity and that this will do more good and lead to more focused and appropriate action and citizens better prepared to do something about our collective dysfunction rather than simply being caught-up on the latest world-wide atrocities.

So, what to do:

1) Turn off and tune out.

• Eliminate all forms of advertising. This means ad-blockers on your phone and computer, fast-forward or mute TV, Youtube, and Podcast-based advertising. Be vigilant with what messaging you allow in your space. You basically want to get to Ad Zero. Support publishers by subscribing to their add-free content (ahem Medium). Its a win-win because the ad rates are a race to the bottom for the publishers and the advertsing itself is a race to the bottom for the viewer/reader.
• Stop watching/reading the news. Check in once a week if needed. Really, if there is anything that you must know it will get to you. I promise. If that seems too daunting, restrict your news to narrow segments that you are interested in. Do you need to be fed photos of a bombing in Libya when you’re simply looking for the Giants score? Get rid of Google News and pick a handful of news sources that are narrowly focused on your interests. Use RSS feeds to follow only the publications/authors/topics that are relevant to you. Narrowcast! Don’t let the media broadcast to you every piece of attrocity going on around the world. Remember its in their interest to do this but it is definitely not in yours.
• Delete the Facebook app from your phone. Seriously. Get rid of it. You can always check from your computer and much less likely to do so compulsively. If you need the messenging function for communication, just keep FB Messenger on your phone. If you are a Twitter junkie, do the same. I would say the same for Instagram and Snapchat, but I know that is a social death sentence for certain demographics.
• Turn off all phone-based notifications if they aren’t personal communications from actual human acquaintances (i.e. except txt, phone, or personal email messages). This alone will make a big difference in your concentration, focus, and clarity. Don’t let the technology make the decision for you. Just because every app encourages push notifications doesn’t mean you have to accept them. Take charge and cut out the notifications for the truly important things like personal or work communication.

2) Take action on things that matter

• Volunteer with or join a cause/community group addressing issues that you are passionate about. If the news of the day is bumming you out, join a group and actively participate in the solution (don’t just send in a donation, it’s not the same thing.) There are groups in every major city addressing political issues, economic issues, social justice issues, poverty, homelessness, you name it.
• Do things that actually are shown to relax your stress response, such as exercise, yoga, meditation, walking in nature. You may notice most of these involve your body, not your mind. Give your mind a break and do something with your body. They both will thank you.
• Take a class or workshop of some kind. Learn something new that will help you or the world in some way. Yes, you have time for it.

3) Connect to real people, real things.

• Meet a friend in person. Have an actual phone conversation with a loved one you don’t see very often.
• Make time for physical intimacy and connection. This can be with a lover, a dog, or even a massage. Physical contact is an important human need and is different than sexual needs.
• Plug in to a community group with shared interests. The key is that you be in-person connceting to actual live humans. (see step 2)
• Spend some time in nature. Leave the phone at home. Connect to the forest, the ocean, or the mountains. The natural world offers mircaulous benefits in terms of stress reduction. We are evolved to feel at home in nature. Our genes crave it.

This combination reverses the learned helplessness, puts you in the driver’s seat of content, messaging, and programming that you are exposing yourself to, and helps you to meet the core needs of connectedness that are much more satisfying, life-affirming and longer-lasting than compulsive consumption-based endorphin and dopamine seeking.