The Mind-Gut Connection: How the Hidden Conversation Within Our Bodies Impacts Our Mood, Our Choices, and Our Overall Health

by Emeran Mayer

became obvious to me that a diet that is high in plant-based complex carbohydrates (from a large variety of different plants), plant-derived fat, grains, naturally fermented foods, and fish, and low in red meat, animal-derived fat, refined sugars, and processed food is the blueprint for most healthy diets around the world. Even better, if you add the benefits of polyphenols (molecules with health-promoting effects that are largely processed by the gut microbiota) contained in olive oil and red wine, certain plant products with anti-inflammatory effects such as turmeric, curcumin, and ginger, and a large number of fermented foods teeming with microorganisms, you have a simple road map for a diet that is good for your microbes (increases the diversity, abundance, and populations of health-promoting microbes), good for your gut (reduces intestinal permeability, e.g., improves a leaky gut), and good for your brain (prevents low-grade immune activation in your brain).

We are just beginning to realize that the gut, the microbes living in it—the gut microbiota—and the signaling molecules that they produce from their vast number of genes—the microbiome—constitute one of the major components of these regulatory systems.

Medicine was already using a similar strategy successfully to combat infectious diseases, unleashing broad-spectrum antibiotics—antibiotics that can kill or cripple many species of bacteria—to wipe out disease-causing bacteria. In both cases, as long as victory could be achieved, collateral damage became an acceptable risk.

ranked the U.S. health care system as the most expensive per capita among eleven Western countries, about two times higher than all the other surveyed countries. At the same time, the United States came in last in overall performance. This data reflects the hard fact that despite the ever-increasing amount of resources spent on dealing with our nation’s health problems, we have made little progress in treating chronic pain conditions, brain-gut disorders such as irritable bowel syndrome (IBS), or mental illnesses such as clinical depression, anxiety, or neurodegenerative disorders.

Since the 1970s, we have also been witnessing new challenges to our health, including the rapid rise of obesity and related metabolic disorders, autoimmune disorders such as inflammatory bowel diseases, asthma, and allergies, and diseases of the developing and the aging brain, such as autism, Alzheimer’s, and Parkinson’s disease.

Your gut has capabilities that surpass all your 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 often referred to in the media as the “second brain.” This second brain is made up of 50-100 million nerve cells, as many as are contained in your spinal cord. The immune cells residing in your gut make up the largest component of your body’s immune system; in other words, there are more immune cells living in the wall of your gut than circulating in the blood or residing in your bone marrow. And there is a good reason for the massing of these cells in this particular location, which is exposed to many potentially lethal microorganisms contained in what we eat.

The lining of your gut is studded with a huge number of endocrine cells, specialized cells that contain up to twenty different types of hormones that can be released into the bloodstream if called upon.

The gut is also the largest storage facility for serotonin in our body. Ninety-five percent of the body’s serotonin is stored in these warehouses. Serotonin is a signaling molecule that plays a crucial role within the gut-brain axis: It is not only essential for normal intestinal functions, such as the coordinated contractions that move food through our digestive system, but it also plays a crucial role in such vital functions as sleep, appetite, pain sensitivity, mood, and overall well-being.

the bacteria, archaea, fungi, and viruses that live inside the gut, which are collectively called the gut microbiota.

More than 100 trillion microbes live in the dark and nearly oxygen-free world of the human gut—about the same number of all the human cells in the body, if you include the human red blood cells in this comparison. This means that only 10 percent of the cells in or on a human being are actually human. (If you include the body’s red blood cells, this number may be closer to 50 percent). If you put all your gut microbes together and shaped them into an organ, it would weigh between 2 and 6 pounds—on par with the brain, which weighs in at 2.6 pounds.

The only currently available way to restore gut microbial diversity in these patients is the transfer of an intact microbiota from the feces of a healthy donor into the gut of the affected patient. This treatment, so-called fecal microbial transplantation, results in an almost miraculous reconstitution of the patient’s own microbial composition. We will learn more about this new type of treatment later in this book.

Up to 15 percent of the population worldwide suffers from the cardinal IBS symptoms, altered bowel habits, and abdominal pain and discomfort. Several studies have reported altered gut microbial communities in a subset of patients, but it’s not clear yet which of the available therapies that aim to restore balance to these gut microbiota (including antibiotics, probiotics, a special diet, or fecal microbial transplantation) work best in individual patients.

Thus, what starts as an emotion in the brain influences your gut and the signals generated by your microbes, and these signals in turn communicate back to the brain, reinforcing and sometimes even prolonging the emotional state.

As autism spectrum disorders rose, so did other diseases linked to a change in our gut microbiota, including autoimmune and metabolic disorders. The similarities in the time course of these new epidemics suggested a common underlying mechanism related to a change in our gut microbiota during the last fifty years. Changes in our lifestyles, diet, and in the widespread use of antibiotics have been implicated as possible causes.

Gut microbiota have also been linked to depression, which is the second leading cause of disability in the United States. The drugs used most often to treat depression are the so-called selective serotonin reuptake inhibitors such as Prozac, Paxil, and Celexa. These drugs boost the activity of the serotonin signaling system, which psychiatry had long thought is exclusively located in the brain. However, we know today that 95 percent of the body’s serotonin is actually contained in specialized cells in the gut, and these serotonin-containing cells are influenced by what we eat, by chemicals released from certain species of gut microbes, and by signals that the brain sends to them, informing them about our emotional state. What is most remarkable is that these cells are tightly connected to sensory nerves that signal directly back into the brain’s emotion regulating centers, making them an important hub within the gut-brain axis. Because of this strategic location it is likely that gut microbes and their metabolites play an important and largely unrecognized role in the development of depression as well as its severity and length—an intriguing possibility that, if confirmed in controlled studies, could create new opportunities for the development of more effective treatments, including specific dietary interventions.

The well-being of your gut microbes depends on the food you eat, and they are more or less programmed in their food preferences during the first few years in life. However, regardless of their original programming, they can digest virtually everything you feed them, regardless of whether you’re an omnivore or a pescatarian. No matter what you feed them, they will use their enormous amount of information stored in their millions of genes to transform partially digested food into hundreds of thousands of metabolites.

similar yet distinct pattern happens when you’re anxious or upset. When you’re depressed, your intestines hardly move at all. In fact, we now know that your gut mirrors every emotion that arises in your brain.

Nearly 15 percent of the U.S. population suffers from a range of aberrant gut reactions, including irritable bowel syndrome, chronic constipation, indigestion, and functional heartburn, which all fall into the category of brain-gut disorders.

Similarly, your enteric nervous system can handle all routine challenges related to digestion. However, when you perceive a threat and feel afraid or angry, the emotional brain center does not send individual instructions to every single cell in the gastrointestinal tract. Instead, the brain’s emotional circuits signal the enteric nervous system to divert from its daily routine. The digestive system switches back to local control once the emotion has passed.

The brain sends two sets of nerve signals: those that stimulate (carried by the parasympathetic nerves, including the vagus nerve) and those that inhibit gut function (the sympathetic nerves). Usually activated in tandem, the two nerve pathways do a remarkable job of adjusting, fine-tuning, and coordinating the activities of the enteric nervous system to shape gut activity reflecting a particular emotion.

Gut cells in a chronically angry or anxious person, using a script that dates back to childhood, may play out dark plots day after day. Many gut cells in these people over time adapt to accommodate the stage directions: nerve connections in the enteric nervous system change, the sensors in the gut become more sensitive, the gut’s serotonin-producing machinery shifts into higher gear, and even gut microbes become more aggressive.

For example, you may have inherited genes that predispose your fear or anger program to overreact to stressful situations. If you also experienced emotional trauma as a child, your body added chemical tags to these key stress-response genes. The net result is that as an adult, you will most likely experience exaggerated gut reactions to stress.

The brain’s dedicated signaling molecules include a few hormones you’ve probably heard about before—endorphins, which act as a painkiller in the body and promotes a feeling of well-being; dopamine, which triggers desire and motivation; and oxytocin, which is sometimes called the “love hormone” and stimulates feelings of trust and attraction.

Ninety percent of the signals conveyed through the vagus nerve travel from the gut to the brain, while just 10 percent of the traffic runs in the opposite direction, from the brain to the gut. In fact, the gut can handle most of its activities without any interference from the brain, while the brain seems to depend greatly on vital information from the gut.

The taste receptors on your tongue can detect five distinct taste qualities, including sweet, bitter, savory, sour, and umami; the combination of these qualities in any bite of food determines its flavor. In addition, the texture of what you eat—the crunchiness of a carrot, the smoothness of yogurt, or the unique texture of a spaghetti squash—stimulates another set of receptors, which specialize in recognizing mechanical qualities of food. The combination of all of these sensations encoded in your mouth creates the experience that you know as taste. Food companies are masters in designing foods that maximize this experience.

recent research has shown that some of the same mechanisms and molecules that are involved in the taste experience are not limited to your mouth, but are also distributed throughout our gastrointestinal tract. Science has unequivocally shown that this is the case for the bitter and sweet taste receptors. In fact, evidence for some twenty-five different bitter taste receptors has been found in the human gut.

For example, does the consumption of spicy foods in many parts of the developing world protect people from gastrointestinal infections? And does the consumption of fresh herbs in Persian dishes, or the obligatory consumption of peppermint tea after a meal in Morocco, prevent indigestion? Regardless of how we explain their prevalent use all over the world, these plant-derived substances link us and our gut-brain axis closely to the diversity of plants around

Even more intriguing is the recent evidence that the same nasal olfactory receptors we use to enjoy the smell of roses, detect a carton of spoiled milk, or sniff out a good barbecue joint are also spread throughout the intestinal

Since taste and olfactory receptors are located throughout the GI tract, rather than only in the mouth and nose, their original names—“taste” and “smell”—have become somewhat obsolete.

For example, when your stomach is empty, specialized cells in the stomach wall produce a hormone called ghrelin, which travels via your bloodstream or signals via the vagus nerve to your brain, where it triggers a strong urge to eat. On the other hand, when you’re satiated and your small intestine is busy digesting your food, cells there release “satiety” hormones that tell your brain that you’re full and it’s time to call a halt to further eating.

This is an inbuilt survival mechanism: when your gut detects enough of a toxin or pathogen, your enteric nervous system issues an evacuation order to your entire GI tract aimed at expelling the toxin from both ends of your digestive tract—a smart reaction, if not a pretty one.

And contrary to the view of the great majority of psychiatrists and most of my gastroenterology colleagues, I suspected early on that modifications in this communication system might even be involved in such nondigestive disorders as anxiety, depression, and autism.

The vast majority of gut microbes are not only harmless, but are in fact beneficial for our health and well-being; these are referred to by scientists as symbionts or commensals. The symbionts obtain nutrients from their hosts, and in exchange they help keep the gut in balance and defend against intruders. But there is a small number of potentially harmful microbes, called pathobionts, that reside in your gut as well. Under certain conditions, these untrustworthy microbes can turn their weapons against

Yet human gut microbes rarely resort to such aggressive tactics. Instead, they usually live in harmony with us, minding their own affairs, which include digestion, growth, and reproduction. Nor does our immune system turn its formidable weapons on gut microbiota.

In exchange, the microbes provide us with essential vitamins, metabolize digestive compounds, called bile acids, that are produced by the liver, and detoxify foreign chemicals that our bodies have never experienced—so-called xenobiotics. Most important, they digest dietary fiber and complex sugar molecules that our digestive system can’t break down or absorb on its own, and thus provide us with a substantial number of additional calories that we would otherwise lose in our stool.

Some of these metabolites can increase the production of serotonin in enterochromaffin cells, making more of this molecule available for signaling to the brain via the vagus nerve.

The Drama of the Gifted Child,

For example, rodents, like people, have different temperaments: some are timid, others are social; some are intrepid explorers, others stick close to home. And some rat mothers—even genetically identical animals—are better than others at nurturing their offspring. A nurturing rat mom pampers her pups. She hovers over them with her back conspicuously arched and legs splayed outward, allowing them to switch nipples, and she spends a lot of time licking and grooming them. A more negligent rat mom lazes on her side or lies on top of her pups as they struggle to nurse.

And keep in mind that the time window during which the development of the stress system is impacted by outside influences lasts up to twenty years in humans.

What are the implications of these laboratory studies for women experiencing pregnancy and motherhood today? Many adult brain disorders, including anxiety, depression, schizophrenia, autism, and most likely IBS, are now considered neurodevelopmental disorders, meaning that the basic brain changes start very early in life, many of them already in utero. As we have learned, stress is a major factor that influences these neurodevelopment changes, and there are at least two major pathways by which early adversity can affect the brain-gut axis: one is by epigenetic modification of the stress response system and the brain-gut axis; the other one is through stress-induced changes in the gut microbiota and their products, which can further affect the brain.

Here was a child being born naturally, without any help or medical intervention, and so quietly that no one else in the entire village seemed to notice. The circumstances of this childbirth were a world away from our modern hospital deliveries, which I had experienced during my medical training: no sterile hospital environment, no ob-gyns to treat the mother’s vagina with antiseptics to “cleanse” it of microbes. Instead the newest Yanomami had been exposed not only to the mother’s vaginal microbiome but also to all the microbes on her (unwashed and unsanitized) hands, on the banana leaf and in the soil. Yet over the next weeks, the baby cuddled by both parents seemed perfectly healthy.

Even in healthy pregnancies, maternal gut bacteria—most of them beneficial—have turned up in umbilical cord blood, amniotic fluid, meconium, and on the placenta, according to recent work. As the time of delivery nears, the vaginal microbiota changes a great deal. The diversity of microbial species decreases, and a lactobacillus species normally found in the small intestine becomes more prevalent. During birth, a baby born naturally is exposed to the mother’s vaginal microbiota, including this lactobacillus species, providing the key source of microbes to colonize the infant’s gut. In this way, your mother’s distinct set of vaginal microbes formed the basis for your own distinct pattern of gut microbes, and will for the rest of your life. The mother’s microbes also supply our newborns with a key piece of its metabolic machinery, giving the baby the ability to digest the milk sugars and special carbohydrates in breast milk.

scientists are now studying whether cesarean delivery jeopardizes a newborn’s future brain health. It is amazing that in such countries as Brazil and Italy the rates of C-section delivered babies surpass those who come into this world in the natural way, even though we have no clue about the long-term consequences of “bypassing” the normal vaginally mediated gut microbiome programming on brain development. So far we know that the intestines of cesarean-born infants are colonized not by the mother’s vaginal microbes, but by microbes from the mother’s skin, from midwives, physicians, and nurses, and from other newborns in the maternity ward, and that important beneficial bacteria such as bifidobacteria take longer to colonize their guts than they do the guts of babies born vaginally.

Scientists suspect that C-section birth may also make a child more vulnerable to brain-gut changes and serious brain disorders, including autism, and several studies are under way to find out for sure.

And we don’t yet know the degree to which practices that alter the vaginal microbiome, such as antimicrobials before and during delivery, birth by cesarean section, or a young mother’s diet and stress, jeopardize a child’s health.

I told her that the bad news is that her brain-gut axis had been programmed for life, but the good news is that humans have a very unique part of the brain, the prefrontal cortex, which gives us the ability to override the function of altered brain circuits and learn new behaviors.

And, if appropriate for the patient, full doses of modern antidepressants, including SSRIs, can ease anxiety and depression and stabilize mood. These drugs by themselves provide significant benefit in about 30 percent of patients, but the success rate is much higher when combined with other, nonpharmacological treatments. Based on our new scientific insights into the role of gut microbiota in the altered brain-gut interactions, I also told Jennifer to increase her intake of probiotics. Beneficial microbes such as lactobacilli and bifidobacteria delivered via fermented foods, yogurts, or in probiotic capsules may improve the diversity of the gut microbial ecosystem.

I encouraged her to eat and drink a wide variety of fermented foods of all types, including yogurt, sauerkraut, and kimchi, and to take additional probiotic supplements as well.

Previous studies had shown that certain microorganisms are able to produce the neurotransmitter gamma-aminobutyric acid. This substance, also referred to as GABA, is one of the most abundant signaling molecules in the nervous system, where it keeps the emotional part of our brain, the limbic system, in check. Many of our antianxiety medications, such as Valium, Xanax, and Klonopin, target the same signaling system, mimicking the effects of GABA.

We know that certain strains of two of the best-studied families of beneficial gut bacteria, the lactobacilli and the bifidobacteria, have the synthetic machinery to produce GABA. Since different strains of bacteria from these two families are active ingredients in most commercially available probiotics, and both groups also tend to be abundant in fermented food products, is it possible that adding an extra supply of these microbes to our diet makes us more relaxed? Could a regimen as simple as eating fermented foods and taking probiotics help anxiety-prone individuals reduce their anxiety levels?