Depression, Serotonin, and the Mind-Gut Connection

Neuroscientists now think of the gut as a "second brain"; it independently controls your digestive processes and is in constant conversation with your main brain. What do they talk about? Depression, theorizes Dr Emeran Mayer.

Emeran Mayer: The Mind-Gut Connection is something that people have intuitively known for a long time but science has only I would say in the last few years gotten a grasp and acceptance of this concept. It essentially means that your brain has intimate connections with the gut and another entity in our gut, the second brain, which is about 100 million nerve cells that are sandwiched in between the layers of the gut. And they can do a lot of things on their own in terms of regulating our digestive processes. But there’s a very intimate conversation between that little brain, the second brain in the gut and our main brain. They use the same neurotransmitters. They’re connected by nerve pathways. And so we have really an integrated system from our brain to the little brain in the gut and it goes in both directions.

The little brain, or the second brain, in the gut you’re not able to see it because as I said it’s spread out through the entire length of the gut from your esophagus to the end of your large intestine, several layers of nerve cells interconnected. And what they do is even if you – and you can do this in animal experiments if you completely disconnect this little brain in the gut from your main brain this little brain can completely take care of all the digestive processes, the contractions, peristaltic reflex, regulation of blood flow in the intestine. And it has many sensors so it knows exactly what’s going on inside the gut, what goes on in the wall of the gut, any distention, any chemicals. All of this is being picked up by these sensory nerves, fed into the interior nervous system, the second brain. And then the second brain generates these stereotypic responses. So when you vomit, when you have diarrhea, when you have normal digestion, all of this is encoded in programs in your second brain.

What the second brain can’t do it cannot generate any conscious perceptions or gut feelings. That really is the only ability that allows us to do this and perceive all the stuff that goes on inside of us is really the big brain and the specific areas and circuits within the brain that process information that comes up from the gut. Still most of that information is not really consciously perceived. So 95 percent of all this massive amount of information coming from the gut is processed, integrated with other inputs that the brain gets from the outside, from smell, visual stimuli. And only a very small portion is then actually made conscious. So when you feel good after a meal or when you ate the wrong thing and you’re nauseated those are the few occasions where actually we realize and become aware of our gut feelings. Even though a lot of other stuff is going on in this brain-gut access all the time.

When we talk about the connection between depression and the gut there’s some very intriguing observations both clinically but also now more recently scientifically that make it highly plausible that there is an integrate connection between serotonin in the gut, serotonin in our food, depression and gut function.

On a clinical level there’s a connection because many patients with depression also complain of constipation. So a distinct dysfunction of the gut. And often the medications that people with depression take, particularly the serotonin reuptake inhibitors such as Prozac and all the other drugs in this category, they often cause transient gastrointestinal dysfunction. So that’s on the clinical level. However, what makes it particularly interesting and still an open question really more than 95 percent of all our serotonin we have in our organism is really produced and stored in the gut in specialized cells, so-called enterochromaffin cells. So our major by far the largest store of that molecule that plays such a big role in modulating our mood and our wellbeing, also appetite, pain, sensitivity is stored in the gut. And a lot of very interesting discoveries have been made more recently that makes this even more intriguing. So this serotonin is synthesized in the gut from precursors that come from our food that we ingest and the microbes that live in the gut are actually able through chemicals that they produce to stimulate the production of serotonin.

It’s been estimated based on studies in animals that 60 percent of the production is due to these signals that come from the microbes that live in our gut. So in addition another intriguing finding is that these serotonin cells, so they’re sandwiched in between the cells that make the lining of the gut. One end sticks into the inside samples, everything that goes on inside the gut. The other side very interestingly has an outgrowth which connected through a synapse with sensory nerve endings. So many vagal nerve endings. So this is a cell that sticks into the gut, samples a lot of things that go on in our digestive tract. Then it produces serotonin largely through the influence of microbes that live in our gut and then the signal when this cell is activated there’s many things chemical or mechanical stimuli associated with digestion. It signals through this synapse directly into our brain through the vagus nerve into centers that have to do with – I mean ultimately with emotional regulation and emotion generation. So even though we don’t have the proof for that it would be very difficult to mention that there’s not a significant influence on our mood and that this system if it’s out of balance does not play a significant role in the pathophysiology of depression.

There’s many food items that contain neuroreactive molecules signaling substances including oysters, chocolate and many other foods that to varying degrees contain either the precursors of serotonin or actually serotonin molecules. It’s possible that these contents of this molecule are the basis for some of these claimed effects of food items like oysters as an aphrodisiac or mood enhancer like with chocolate. People say they feel a lot better after they eat their daily piece of chocolate in the evening which is pretty true. Not just from the taste but from this chemical connection.

We all feel things in our gut – intuitions that give us subtle physiological alerts, stress and anxiety that unsettle us, bad reactions to food, and conversely feelings of contentment from the right food, or flutters from an exciting experience. But according to Dr Emeran Mayer, what we feel is just a small fraction of what’s going on in a region of our body that is still quite mysterious – even to the experts.


In his new book, The Mind-Gut Connection,, Dr Mayer writes: "Your gut has capabilities that surpass all our other organs and even rival your brain. It has its own nervous system, known in scientific literature as the enteric nervous system, or ENS, and [is] often referred to in the media as the "second brain.""

As Mayer describes, this second brain consists of about 100 million nerve cells sandwiched between layers of the gut running all the way from the esophagus to the end of the large intestine. This ‘second brain’ and our regular brain use the same neurotransmitters and are connected through neural, endocrine, and immune pathways, so it truly is an integrated intelligent system with information flowing in both directions.

What makes the second brain unique from other organs is that – in animals at least – when it’s separated from the main brain it continues to pilot its complex activities on its own.

The system is extremely interesting to researchers because of this independent streak, and the effect that it may have on our mental health. After his many years of research, Mayer humbly says it’s "highly plausible" that there is a connection between the gut and mental health conditions such as depression. Scientists from the University of North Carolina have found that gut bacteria produce neurotransmitters like serotonin, dopamine and GABA, all of which have associations with our mood. Often the medications people with depression take are designed to adjust the uptake of these neurotransmitters, a treatment scientists at the time designed thinking only of the brain, but it may now also have implications in the microbiome.

What makes it even more intriguing is that more than 95% of our body’s serotonin is produced and stored in the gut in specialized enterochromaffin cells, says Dr Mayer, adding: "By far the largest store of the molecule that plays such a big role in modulating our mood and our wellbeing – also appetite, pain sensitivity – is stored in the gut."

In recent years, the microbiome has come to the fore of scientific research, hinting at the wide reach of its sway over the body and mind. There is still a long, long way to go in understanding direct causations, but when that happens, there is no doubt our comprehension of this second brain will affect our well-being and quality of life in a big way.

Dr Emeran Mayer's most recent book is The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health

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Why Epicurean ideas suit the challenges of modern secular life

Sure, Epicureans focused on seeking pleasure – but they also did so much more.

Antonio Masiello/Getty Images
Culture & Religion

'The pursuit of Happiness' is a famous phrase in a famous document, the United States Declaration of Independence (1776). But few know that its author was inspired by an ancient Greek philosopher, Epicurus. Thomas Jefferson considered himself an Epicurean. He probably found the phrase in John Locke, who, like Thomas Hobbes, David Hume and Adam Smith, had also been influenced by Epicurus.

Nowadays, educated English-speaking urbanites might call you an epicure if you complain to a waiter about over-salted soup, and stoical if you don't. In the popular mind, an epicure fine-tunes pleasure, consuming beautifully, while a stoic lives a life of virtue, pleasure sublimated for good. But this doesn't do justice to Epicurus, who came closest of all the ancient philosophers to understanding the challenges of modern secular life.

Epicureanism competed with Stoicism to dominate Greek and Roman culture. Born in 341 BCE, only six years after Plato's death, Epicurus came of age at a good time to achieve influence. He was 18 when Alexander the Great died at the tail end of classical Greece – identified through its collection of independent city-states – and the emergence of the dynastic rule that spread across the Persian Empire. Zeno, who founded Stoicism in Cyprus and later taught it in Athens, lived during the same period. Later, the Roman Stoic Seneca both critiqued Epicurus and quoted him favourably.

Today, these two great contesting philosophies of ancient times have been reduced to attitudes about comfort and pleasure – will you send back the soup or not? That very misunderstanding tells me that Epicurean ideas won, hands down, though bowdlerised, without the full logic of the philosophy. Epicureans were concerned with how people felt. The Stoics focused on a hierarchy of value. If the Stoics had won, stoical would now mean noble and an epicure would be trivial.

Epicureans did focus on seeking pleasure – but they did so much more. They talked as much about reducing pain – and even more about being rational. They were interested in intelligent living, an idea that has evolved in our day to mean knowledgeable consumption. But equating knowing what will make you happiest with knowing the best wine means Epicurus is misunderstood.

The rationality he wedded to democracy relied on science. We now know Epicurus mainly through a poem, De rerum natura, or 'On the Nature of Things', a 7,400 line exposition by the Roman philosopher Lucretius, who lived c250 years after Epicurus. The poem was circulated only among a small number of people of letters until it was said to be rediscovered in the 15th century, when it radically challenged Christianity.

Its principles read as astonishingly modern, down to the physics. In six books, Lucretius states that everything is made of invisible particles, space and time are infinite, nature is an endless experiment, human society began as a battle to survive, there is no afterlife, religions are cruel delusions, and the universe has no clear purpose. The world is material – with a smidgen of free will. How should we live? Rationally, by dropping illusion. False ideas largely make us unhappy. If we minimise the pain they cause, we maximise our pleasure.

Secular moderns are so Epicurean that we might not hear this thunderclap. He didn't stress perfectionism or fine discriminations in pleasure – sending back the soup. He understood what the Buddhists call samsara, the suffering of endless craving. Pleasures are poisoned when we require that they do not end. So, for example, it is natural to enjoy sex, but sex will make you unhappy if you hope to possess your lover for all time.

Epicurus also seems uncannily modern in his attitude to parenting. Children are likely to bring at least as much pain as pleasure, he noted, so you might want to skip it. Modern couples who choose to be 'child-free' fit within the largely Epicurean culture we have today. Does it make sense to tell people to pursue their happiness and then expect them to take on decades of responsibility for other humans? Well, maybe, if you seek meaning. Our idea of meaning is something like the virtue embraced by the Stoics, who claimed it would bring you happiness.

Both the Stoics and the Epicureans understood that some good things are better than others. Thus you necessarily run into choices, and the need to forgo one good to protect or gain another. When you make those choices wisely, you'll be happier. But the Stoics think you'll be acting in line with a grand plan by a just grand designer, and the Epicureans don't.

As secular moderns, we pursue short-term happiness and achieve deeper pleasure in work well done. We seek the esteem of peers. It all makes sense in the light of science, which has documented that happiness for most of us arises from social ties – not the perfect rose garden or a closet of haute couture. Epicurus would not only appreciate the science, but was a big fan of friendship.

The Stoics and Epicureans diverge when it comes to politics. Epicurus thought politics brought only frustration. The Stoics believed that you should engage in politics as virtuously as you can. Here in the US where I live, half the country refrains from voting in non-presidential years, which seems Epicurean at heart.

Yet Epicurus was a democrat. In a garden on the outskirts of Athens, he set up a school scandalously open to women and slaves – a practice that his contemporaries saw as proof of his depravity. When Jefferson advocated education for American slaves, he might have had Epicurus in mind.

I imagine Epicurus would see far more consumption than necessary in my own American life and too little self-discipline. Above all, he wanted us to take responsibility for our choices. Here he is in his Letter to Menoeceus:

For it is not drinking bouts and continuous partying and enjoying boys and women, or consuming fish and the other dainties of an extravagant table, which produce the pleasant life, but sober calculation which searches out the reasons for every choice and avoidance and drives out the opinions which are the source of the greatest turmoil for men's souls.

Do you see the 'pursuit of happiness' as a tough research project and kick yourself when you're glum? You're Epicurean. We think of the Stoics as tougher, but they provided the comfort of faith. Accept your fate, they said. Epicurus said: It's a mess. Be smarter than the rest of them. How modern can you get?Aeon counter – do not remove

This article was originally published at Aeon and has been republished under Creative Commons. Read the original article.


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