How Your Gut Talks to Your Brain
From morning to night, as you wrestle with the responsibilities of everyday life, how often do you think about what’s happening in your belly? If you’re like most people, probably not much. But as quietly as our guts usually go about their business, the events in your stomach and intestines are momentous. To get a firsthand impression of these gut sensations, try this experiment: take a day when you’re not too distracted, and focus your attention from morning to night on all the sensations that your gut generates throughout the day.
These are the sensations you normally wouldn’t pay much attention to—the subtle physical feelings and sounds, as well as the background emotions that accompany them. Try to be mindful of as many of these sensations as you can, and write them down on a sheet of paper or dictate them into your smartphone as they occur. You may also want to add information about what you were doing at the time, how you were feeling, and what you were eating. Here is an example of such an experiment—one day’s worth of gut sensations performed by Judy, a healthy, twenty-six-year-old research volunteer who participated in a study we conducted many years ago.
Judy wakes up early on Sunday morning, has a cup of coffee, then goes on her daily morning run. She doesn’t eat anything before the three-mile run because she knows from experience that running on a full stomach interferes with her exercise. When she returns from her run, she makes her weekly phone calls to her mother and to a good friend. By the time she’s done speaking with them, she is starving and craving her usual Sunday breakfast—a mushroom omelet and a fresh sourdough baguette with cream cheese.
She enjoys the breakfast, getting a pleasant feeling from savoring this favorite meal. At the same time, she doesn’t pay that much attention to what she’s eating because she is reading an interesting article in the newspaper. At some point she feels full and leaves half of the uneaten omelet on her plate. She has made plans to go bicycling at the beach with her boyfriend, and before she leaves the house, she needs to go to the bathroom for a bowel movement. She and her boyfriend have a great time at the beach. When she gets back home, it’s 7 p.m.
After having a light dinner, Judy realizes that she hasn’t spent any time on a work presentation she has to give on Monday morning. She starts worrying, and notices a queasy feeling in the pit of her stomach. The feeling slowly improves as she tries to finish her presentation and at 10 p.m., she decides to go to bed and get up early the next morning to perfect the presentation. She sets her alarm clock for 5:30 a.m. but doesn’t sleep well. Each time she wakes up, she notices a gurgling sensation in her belly; sometimes it feels like a long, loud rumbling that slowly migrates down the length of her abdomen. She finally gets up, goes to the kitchen, and finishes the leftover omelet from breakfast. The rumbling noises stop, and she feels better and goes back to sleep.
When you think about it, you likely experience similar gut sensations on a daily basis, although you may not be fully aware of them. We’ve all lived with these sensations our entire lives, and they have become second nature. From the perspective of sheer survival, this general lack of attention to and awareness of our gut sensations is a good thing: Navigating the complexities and information overflow of the modern world is hard enough already. Can you imagine spending each day focused on the rumblings and contractions of your gut, or being forced awake every evening when another wave of high-amplitude contractions sweeps through your GI tract? If we had to continuously attend to these sensations we wouldn’t be able to concentrate on anything else. You wouldn’t be able to carry on a dinner conversation, take a nap after lunch, read the New York Times Sunday edition, or sleep through the night.
The only gut sensations that we are generally aware of are those that require a response: a sensation of hunger that prompts us to eat something, a sensation of satiety when it is time to stop eating, or a sensation of fullness in our belly that makes us look for a toilet. We remain blissfully unaware of most gut sensations until we experience some gastro-calamity such as a stomachache, heartburn, nausea, a persistent sense of bloating, or, worse, a bout of food poisoning or a viral gastroenteritis. Or we may just feel we ate too much and feel awful, even after eating a normal-sized meal. Suddenly the sensory information from our gut becomes quite relevant—and usually for good reasons. These unpleasant sensations drive us to seek help, and they help us avoid whatever caused our distress in the future by making sure we never forget.
The Brain That Felt Too Much
While most people are consciously unaware of virtually all their gut sensations, there are some notable exceptions. One involves the very select group of people who are easily able to feel their heartbeats and food moving through their intestines. These individuals show an increased awareness of all signals from their bodies, including those arising from the gut. In brain imaging experiments, they have been shown to have heightened responses of brain networks that are concerned with attention and salience assessment.
The other exceptions to this rule are the unfortunate 10 percent of the population who perceive corrupted signals from their gut that don’t match the actual sensory information transmitted to the brain. Out of the many patients I have seen in my practice, one very pleasant gentleman stands out in terms of his unique history, which illustrates this concept of increased awareness of bodily sensations.
Frank was a seventy-five-year-old retired schoolteacher who came to see me with GI problems he had been experiencing over the last five years, including typical IBS symptoms of abdominal bloating and discomfort, and irregular bowel movements. However, the IBS symptoms were not his only problem. He also experienced a chronic, unpleasant sensation that felt as if something were stuck in the upper part of his esophagus (so called globus sensation), frequent episodes of belching, sensations of discomfort behind his sternum (his chest bone) that sometimes had a menthol-like quality and made him cough, and the sensation of not getting enough air when taking a breath. These symptoms started suddenly about five years before he came to see me. The onset of his symptoms coincided with the loss of his wife due to a serious illness.
When I pressed for more information that would help me make a diagnosis, Frank admitted that he had been experiencing mild IBS like symptoms since childhood. As Frank had undergone repeated extensive diagnostic evaluations of his chest, his gastrointestinal tract, and his heart, which did not reveal any plausible cause for his symptoms, it seemed most likely that he was suffering from some sort of functional gastrointestinal disorder. His symptoms were most consistent with a generalized hypersensitivity to gut sensations coming from different regions of his gastrointestinal tract, from the beginning of his esophagus all the way to the end of his colon. While some physicians might dismiss his symptoms as purely psychological in nature, we now know that there is an elaborate sensory machinery located in our gastrointestinal tract, including the specialized molecules (so-called receptors) that can recognize different chemicals including menthol. But what could have triggered this hypersensitivity in Frank five years ago?
Frank’s partner provided one potential explanation: Frank had long been eating an unhealthy diet, including foods high in animal fats and sugar. She had noticed that his symptoms got worse when he couldn’t control his craving for chocolate cake, pizza, french fries, or rich cheeses. Is it possible that these high-fat food items may have played a role in the sensitization of his gut-brain communication? Patients like Frank are not only more sensitive to normal gut functions, such as contractions, distensions, and acid secretion. We know from many studies in patients like Frank that some of them are also more sensitive to experimental stimuli such as inflating a balloon in their intestine, or exposing their esophagus to an acidic solution.
Given the complexity of the gut’s sensory system, it is no surprise that this system is vulnerable to disturbances, like overreacting to normal food components, or being hypersensitive to food additives or changes in food supply that may not be good for us, but which are tolerated by the majority of people without any symptoms. Could it be that people like Frank are the canaries in the coal mine, the first to be affected by some pending calamity?
More than 90 percent of the sensory information collected by your gut never reaches conscious awareness. For most of us it’s easy to ignore the daily sensations from our belly; yet the enteric nervous system is monitoring them very carefully. Through a complex system of sensory mechanisms, many of your gut sensations are quietly directed to the little brain in your gut, providing it with vital information to ensure optimal functioning of your digestive system twenty-four hours a day. But a huge flow of gut sensations is also directed upward, to the brain. 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.
What information is your gut reporting on that’s so vital? Far more than you might imagine. The many sensors in your gut inform the enteric nervous system about everything it needs to know in order to generate the most appropriate pattern of contractions, that is, the strength and direction of the gut’s peristalsis to speed or slow the transit of ingested food through the stomach and intestine, and to produce the right amount of acid and bile to ensure proper digestion. It gathers information pertaining to the presence and amount of food in the stomach, the size and consistency of the food you swallow, the chemical composition of an ingested meal, and even the presence and activity of your community of gut microbiota. In case of an emergency, these sensors will also detect the presence of parasites, viruses, or pathogenic bacteria, or their toxins, as well as the gut’s inflammatory response. In fact, acute gut inflammation will make many of the sensors more sensitive to normal stimuli and events. While this information is vital to ensure proper functioning of the digestive tract, the enteric nervous system has no ability to produce conscious sensations. When Gershon’s book, The Second Brain, came out, it sparked much speculation about the abilities of the enteric nervous system. Some even wondered if the second brain not only is capable of perception, but may also be the seat of our emotions and our unconscious mind. However, we can almost certainly say that these speculations were false. The sensory information from the gut is also sent to the brain in your head, and if you pay attention to these sensations you will be able to feel them.
Twenty-four hours a day, seven days a week, our GI tract, enteric nervous system, and brain are in constant communication. And this communication network may be more important for your overall health and well-being than you ever could have imagined.
Sensing with Your Gut
Take a bite of juicy hamburger, enjoy a piece of fresh, crispy baguette, savor a cup of New England clam chowder, or revel in the exquisite flavor of a good piece of chocolate. What do you taste?
The answer will be supplied to you by the collection of receptors located on the taste buds of your tongue. These molecules embedded in the outer membrane of a cell recognize the specific chemicals in anything you eat or drink, as a lock recognizes a key. When this receptor binds to such a chemical on a food item, it sends a message to your brain, and your brain constructs the particular taste from the streams of sensory information it receives from your mouth and tongue.
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.
Amazingly, 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. While we know that the gut taste receptors have little or nothing to do with our taste experience, we also know very little about their functions in the gut-brain axis. However, these receptor molecules are located on sensory nerve endings and on the hormone-containing transducer cells in the gut wall (such as the serotonin-containing cells we discussed in the previous chapter), which puts them in a perfect location to participate in the gut-brain dialogue.
Some of these receptors are activated by specific molecules found in herbs and spices like garlic, hot chili pepper, mustard, and wasabi, while others respond to menthol, camphor, peppermint, cooling agents, and even cannabis. To date, twenty-eight of these so-called phytochemical receptors (receptors that recognize specific chemicals in plants) have been identified in the mouse intestine alone, and there is no reason to doubt that our human intestines have a similar or even greater diversity of receptors that are sensitive to a variety of chemicals contained in plants.
Most of us use spices and herbs to stimulate the taste receptors on our tongues, thereby enhancing the flavor of a meal. A growing number of individuals who believe in natural treatments consume herbs or their extracts specifically for medicinal purposes, and herbologists can tell you a litany of empirically derived health benefits for all of them. However, in many parts of the world, spices are an integral part of the culture: who could imagine Indian or Mexican foods without chili peppers, Persian food without an assortment of fresh herbs and yogurt, or Moroccan tea without peppermint?
It is plausible that regional and geographic differences in people’s taste preferences for various herbs and spices have evolved to encourage their consumption, and provide protection against common illnesses prevalent in different parts of the world. 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 us. The multitude of phytochemicals derived from a diet rich in diverse plants, combined with the array of perfectly matching sensory mechanisms in our gut, synchronizes our internal ecosystem (our gut microbiome) with the world around us.
Why are there so many sensors in our gut? Some receptors, like those that sense for sweet food, play an important role in the way we metabolize our food. When our sweet receptors sense glucose (created when carbohydrates are digested) or artificial sweeteners, they stimulate the absorption of glucose into the bloodstream, and the release of insulin from the pancreas. They also stimulate the release of several other hormones that signal to the brain and create a sense of satiety.
The function of the gut’s bitter taste receptors remains something of a mystery. My colleague Catia Sternini, a neuroscientist at UCLA who’s an expert on the enteric nervous system and who focuses on intestinal taste receptors, speculates that some of these receptors may respond to metabolites produced by intestinal microbiota, and that alterations in these receptors as a consequence of high fat intake and fat-related changes in gut microbiota could play a role in obesity. In a collaborative study, we have recently demonstrated support for this hypothesis in obese subjects.
There are other possible roles that have been proposed for the bitter taste receptors in the gastrointestinal tract. Their stimulation has been shown to result in the release of the gut hormone ghrelin, also known as the hunger hormone, which travels to the brain to stimulate appetite. I wouldn’t be surprised if the ancient habit in many European countries of drinking a bitter aperitif before meals developed because of the aperitifs’ ability to stimulate bitter taste receptors in the gut to release ghrelin and thus increase the appetite.
Think, too, of all the horrendous-tasting bitter herbal medicines employed in traditional Chinese medicine. It seems much more likely that their therapeutic effects have little to do with the bitter taste experience they give you, but are related in some way to the activation of one or more of the gut’s twenty-five bitter receptors, thereby sending healing messages to your brain and body. 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 tract. Like the gut’s taste receptors, these gut olfactory receptors are located primarily on endocrine cells, where they control the release of different hormones.
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. Instead, scientists now understand that these receptors are part of a large family of chemical sensing mechanisms that are found in the lungs and other viscera, and play different roles depending on their location in different organs. Based on what we know today, I wouldn’t be surprised if these chemical sensors are able to pick up messages from the different microbial communities living in these organs.
How does the nervous system obtain its share of this vital information from inside of your messy gut? It would hardly make sense for this high-performance data collection system to be immersed in the messy world of partially digested food and corrosive chemicals moving through the gut. In fact, it’s not: the neurons themselves sit inside the gut lining, out of direct contact with the gut’s contents, and rely on specialized gut-lining cells that do face the inside of the gut to sense events there. Those cells signal to intermediaries in the gut wall, in particular the various endocrine cells that in turn signal to nearby sensory neurons, in particular the vagus nerve. To date, a large number of different sensory neurons have been identified that are each specialized for a specific aspect of gut sensations and respond to a particular molecule released by the gut’s endocrine cells. Each of these nerves will send signals to the enteric nervous system or to the brain.
The gut’s endocrine cells are so abundant and so deft at signaling our nervous system that they play crucial roles in our health and well-being. Imagine for a moment that you could compress all these hormone-containing cells in your gut into one single clump of cells: it would be the biggest endocrine organ in our bodies. Endocrine cells that line the gut from the stomach all the way to the end of the large intestine can sense a wide range of chemicals contained in what we eat and which are produced by the microbiota. 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.
In addition to the gut-brain communication channel involving the endocrine cells, there is another system involving our gut-based immune system and the inflammatory molecules these immune cells produce, the so called cytokines. The immune cells living in our gut are preferentially located in clusters in the small intestine known as Peyer’s patches, and are also found in our appendix and scattered throughout the wall of the small and large intestine. The gut-based immune cells are separated by a tiny layer of cells from the space inside the gut, and some of them, the so-called dendritic cells, even extend through the gut layer, where they can interact with our gut microbes and with potential harmful pathogens. Most important, cytokines released from these cells can cross the gut lining, enter the systemic circulation, and ultimately reach the brain. Alternatively, the signaling molecules released from hormone-containing gut cells signal to the brain via the vagus nerve.
With so many mechanisms involved in informing our nervous system about aspects of the foods we ingest, it is becoming clear that our gut is designed to do far more than just absorb nutrients. The gut’s elaborate sensory systems are the National Security Agency of the human body, gathering information from all areas of the digestive system, including the esophagus, stomach, and intestine, ignoring the great majority of signals, but triggering alarm when something looks suspicious or goes wrong. As it turns out, it’s one of the most complex sensory organs of the body.
Total Gut Awareness
Whenever you consume food or drink, reports from your intestinal data collection system provide a variety of vital information to both the little brain in your gut (your enteric nervous system) and the brain in your head. Your big and little brains are both interested in obtaining these reports whenever you consume food or drink, but they’re interested in different aspects of this information.
Your little brain needs vital information from the gut to generate optimal digestive responses and, when necessary, to eliminate toxins by expelling the intestinal content from either end of the GI tract by vomiting or diarrhea. These reports cover the size of the meal, the contents that are entering the gut (including chemical information such as fat, protein, and carbohydrate content, as well as concentrations, consistencies, and particle sizes). They also include intelligence revealing any signs of hostile intruders such as bacteria, viruses, or other toxins from contaminated food. When it obtains information about the high fat content of a rich dessert entering your stomach, it will slow the rate of gastric emptying and intestinal transit. When it obtains information about the low caloric density of a meal, it will speed up its emptying from the stomach to deliver enough calories for absorption. And when it obtains information about potentially harmful intruders, it will stimulate water secretion, change the direction of peristalsis to empty the stomach from its content, and accelerate the transit throughout the small and large intestine to expel the offending agent.
Your brain, on the other hand, is more concerned with your overall health and well-being and as such it monitors different cues from your gut and integrates them with a variety of signals from other parts of your body as well as information about your environment. It monitors what is going on in the enteric nervous system, but in addition is closely interested in your gut reactions, the state of the gut reflecting your emotions, the wrenching contractions of your stomach and colon when you are angry, and the absence of intestinal activity when you are depressed. In other words, the brain watches its own theater being played out on the stage of the gut. The brain almost certainly also receives information generated by the trillions of microbes living in the gut, an aspect of gut-brain signaling that only came into focus during the past few years. While the brain constantly monitors all sensory information coming from the gut, it delegates the day-to-day responsibilities to local agencies, in our case the enteric nervous system. The brain only gets directly involved in the action if an action is required by you, or if the situation poses a significant threat that warrants a brain response.
Through these various sensory mechanisms, your gut informs your brain every millisecond of the day, whether you’re awake or asleep, about everything taking place deep inside you. It’s not the only organ providing ongoing feedback to the central nervous system: Your brain continually receives sensory information from every cell and organ in your body. Your lungs and diaphragm transmit mechanical signals to the brain every time you inhale and exhale, your heart generates mechanical signals with each heartbeat, your artery walls send signals about blood pressure, and your muscles transmit information about their tone or tightness.
Scientists call these ongoing reports about the state of the body “interoceptive” information—information that the brain then uses to keep the body’s systems balanced and functioning smoothly. Although interoceptive information comes from every single cell of the body, the messages the gut and its sensory mechanisms send to our brain are unique in their sheer number, variety, and complexity. Start with the fact your gut’s sensory network is distributed over the gut’s entire surface area, which is two hundred times larger than the surface area of your skin—about the size of a basketball court. Now imagine a basketball court with millions of tiny mechanical sensors that collect information about the movement of the players, their weight, their acceleration and deceleration, and about every jump and landing. Since the gut’s signals also include chemical, nutritional, and other information, this metaphor only begins to describe the vast amount of information encoded as gut sensations.
The Information Highway for Gut-Brain Traffic
The vagus nerve plays a particularly important role in communicating gut sensations to the brain. The great majority of gut cells and receptors that encode gut sensations are closely linked to the brain via the vagus nerve. And much of the signaling of our gut microbiota to the brain relies on this pathway as well. In the majority of rodent studies on the effects of gut microbial changes on emotional behaviors, the effects were no longer seen after the vagus nerve was cut. But the vagus nerve is more than a one-way communication channel: This nerve is a six-lane freeway, allowing rush hour traffic in both directions, though 90 percent of this traffic flows from gut to brain. The vagus nerve carries so much traffic because it’s one of the most important regulators of our viscera, linking the brain not just to the GI tract but to all other organs as well.
The following patient anecdote illustrates how important this gut-brain communication system is for our overall well-being. During my training at UCLA, I met George Miller, who had long suffered from symptoms of a large ulcer in his duodenum—the first part of the small intestine. Not only was he miserable and in pain whenever his ulcer flared up, but he had to be hospitalized twice when his ulcer started to bleed acutely. After he had been suffering from these symptoms for years, the decision was made by his gastroenterologist to refer him to a surgeon to cut his vagus nerve, thereby removing its ability to stimulate acid production in the stomach. The personal stories and symptom histories experienced by patients like Miller following their vagotomies revealed a great deal about gut sensations and what happens to people when you deprive the brain of this vital source of interoceptive information.
In the early 1980s, the prevailing view in the medical and surgical community was that the simplest and most effective way to stop excess acid production and cure peptic ulcers was to cut the vagus nerve—a procedure known as a truncal vagotomy. These surgeries were done with little consideration for the massive flow of information through the vagus nerve from the gut to the brain, and the possible importance of this information flow to our overall well-being. Fortunately, surgeons rarely resort to such drastic procedures today, since we can now treat the great majority of ulcers medically.
In Miller’s case, his surgery had been successful, in that his ulcer no longer troubled him. But the price he paid was enormous. From that point on, he suffered an array of unpleasant gut sensations. He felt full after even a small meal and endured constant nausea and vomiting, cramps, belly pain, and diarrhea, among other symptoms.
Miller’s doctors could not explain his symptoms, which also included obscure symptoms such as heart palpitations, sweating, lightheadedness, and extreme fatigue, so they blamed his alleged neuroticism and labeled his constellation of symptoms a case of “albatross syndrome,” a term once used to describe patients like Miller whose peptic ulcer surgery successfully treated their gastric ulcers but left them with a range of aversive gut sensation, lasting abdominal pain, nausea, vomiting, and poor food intake. But we now know that for many of these patients at least, their symptoms had a very solid physiological basis.
Today we know about the complexity of gut sensations and the crucial role the vagus nerve plays in transmitting these signals to brain regions like the hypothalamus and limbic brain regions, which in turn influence a wide range of vital functions such as pain, appetite, mood, and even cognitive function. In hindsight, it is easy to see that obstructing this vital information highway (like closing the 405 freeway in Los Angeles in both directions) would have profound effects on how someone feels when they wake up in the morning, or when they eat.
It’s unlikely we’ll ever know the exact mechanisms behind Miller’s symptoms, since vagotomies are rarely performed today. On the other hand, there has been a renewed interest in studying the role of the vagus nerve in transmitting gut sensations to major control centers in the brain. Electrical or pharmacological vagal stimulation has been evaluated as a novel way to simulate gut sensations, and as therapy to treat a range of brain disorders, including depression, epilepsy, chronic pain, obesity, and even various chronic inflammatory diseases such as arthritis. These new findings further confirm the importance of vagal-gut-brain communication to people’s health and well-being.
The Role of Serotonin
Among the most wrenching of gut sensations are those associated with food poisoning, and about forty years ago I became more closely acquainted with them than I had hoped. I was finishing a four-week backpacking trip in India. The journey had taken me past peaceful Buddhist monasteries and peach-tree-covered oases, and through deserted valleys and mountain passes from northern India to the foothills of the Himalayas. I had been subsisting on daily rations of lentil soup, rice, and butter tea, drinking water directly from pristine streams. I’ve rarely felt as elated as I did when I arrived in the hill station city of Manali, and to celebrate I departed from my usual routine and treated myself to a delicious and spicy meal at one of the local restaurants.
Early the next morning, I boarded the bus for a twenty-four-hour ride to New Delhi—a day that shall forever live in digestive infamy. Trying to control the gastrointestinal consequences of that meal was like telling an attacking pack of hyenas to lie down and roll over. The intensity of this experience engraved itself into the deepest layers of my emotional memory—a permanent reminder of just how powerful gut sensations (and their memories) can be.
Food poisoning occurs when you accidentally ingest a drink or a meal contaminated with a pathogenic virus, bacterium, or a toxin produced by these microorganisms. Let’s say it’s the toxin of an invasive species of E. coli. In your intestine, the toxin binds to receptors located on the serotonin-containing cells. This signal immediately switches your GI tract’s setting to “horrific vomiting and hurricane-like diarrhea.” Some cancer chemotherapy drugs, including cisplatin, do the same thing.
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.
The reaction is driven by serotonin-containing cells in the upper gut, which are particularly important in the generation of gut sensations. When secreted under normal conditions, serotonin helps the digestive process proceed in regular fashion. It is released by subtle mechanical shearing forces exerted when the gut’s contents slide along the GI tract and rub against what are known as enterochromaffin cells. Just like the other hormones contained in the endocrine cells of the gut, the released serotonin activates sensory nerve endings in the vagus nerve and the enteric nervous system (ENS), which in turn keep the ENS informed about what is moving down the intestinal tract, enabling it to trigger the all-important peristaltic reflex. A more concentrated serotonin release, such as occurs with food poisoning or in response to the chemotherapeutic agent cisplatin, on the other hand, will lead to vomiting, intensive bowel movements, or both.
My research group, working with a group from the Netherlands, found that in healthy subjects, a diet deficient in the amino acid tryptophan, essential for making serotonin, lowers brain serotonin levels, which increases activity of the brain’s arousal network. These central nervous system changes are also associated with increased sensitivity to an experimental mechanical stimulation of the colon. The same serotonin-lowering diet had previously been shown to increase the likelihood of depression in at-risk individuals, including those with a family history of depression.
Serotonin is the ultimate gut-brain signaling molecule. Serotonin-containing cells are intricately connected to both our little brain in the gut and to our big brain. This gut-based serotonin-signaling system plays a key role in linking events in the gut related to food, intestinal microbes, and certain medications to the activity of our digestive system, and to the way we feel. On the other hand, the small amount of serotonin contained in nerves in the gut and in the brain plays crucial roles as well: serotonin-containing nerves in the gut play a key role in regulating the peristaltic reflex, while clusters of nerve cells in the brain send their signals to most regions of the brain, exerting an influence over a wide range of vital functions, including appetite, pain sensitivity, and mood.
Mike Gershon, pioneering researcher of the gut’s serotonin system, likes to say that the only time you’ll ever be aware of gut sensations related to the gut-serotonin system is when the news is bad—or in some cases very bad, like my hellish bus ride to New Delhi. But is that really so? Let’s leave aside for a moment the dramatic events that unfold when a bacterial or viral infection triggers a massive serotonin release, or when an alteration in the gut’s serotonin system produces IBS symptoms or diarrhea. Given the gut’s enormous serotonin stores, located close to vagal nerve pathways that link directly to the brain’s affective control centers, it’s certainly conceivable that a constant stream of low-level, serotonin-related gut signals are being sent to our brain’s emotional centers, in response to intestinal contents rubbing against the serotonin-packed cells, or in response to gut microbial metabolites. Even if these serotonin-encoded signals don’t enter our conscious awareness, this low-level serotonin release could affect our background emotions and influence how we feel, exerting a positive “tone” on our mood—which in turn could explain why so many people experience a sense of contentment and well-being around the ingestion of an enjoyable meal.
Food as Information
All of this raises an important question: If the great majority of us don’t consciously perceive the vast majority of our gut sensations—including the twofold distension of the stomach after eating a big meal, or the nutcracker-like contractions of the migrating motor complex when our gut is empty—then why does the gut need its specialized sensory apparatus?
The simple and scientifically supported answer is that these sensing mechanisms are essential to the smooth operation and coordination of basic gut functions such as gastric emptying, movement of food through the intestines, and the secretion of acid and digestive enzymes; to body functions related to food intake, such as appetite and satiation; and to our basic metabolism, including blood sugar control. These functional aspects of gut sensations most likely go back millions of years, to when tiny, primitive marine animals were “colonized” by microorganisms that helped them metabolize certain nutrients.
The other, more provocative answer to the question of why this gut sensory system exists has to do with the massive information flow from our gut to our brains—information that is not directly related to our gut functions and our metabolic needs, and that remains largely below our radar screens. The massive amount of gut-related information being sent to the brain, which includes a barrage of messages from the trillions of microbes living in our gut, gives the gut-brain axis a unique and unexpected role in modulating our health and well-being, our feelings, and even—as we’ll see in Chapter 5—the decisions we make.
When we consider the scientific complexities of the various gut sensors and the vagus nerve, together with their functions in the digestive process, and place them into the overall context of gut sensations, a revolutionary picture of our eating habits emerges: not only is our digestive tract able to absorb most of the nutrients and calories contained in a meal (with our intestinal microbes taking care of the leftovers that our gut cannot digest), but the gut’s sophisticated surveillance system can actually analyze food’s nutritional content and, at the same time, extract the information needed for its optimal digestion. In other words, food comes with its own instructions for how to optimally digest it, and with a lot of fine print that until recently we didn’t even know about, and are still trying to figure out the meaning of. This is true whether you are a vegan, pescatarian, omnivore, meat-meister, fast-food junkie, serial dieter, episodic faster—or even if you recently picked up a gut infection while traveling in Mexico. Most remarkably, the gut’s intricate sensory system begins extracting this information the second the food enters our mouth—when taste receptors on our tongue and enteric nerves in our esophagus begin transmitting information about what we’re ingesting—and continues doing so until the food ends up in our colon. And our gut does all this without interfering in any way with our daily functioning.
When we consider the dense distribution and vast area that the gut’s sensory receptors occupy on the lining of our gut wall, it’s clear that our gut is transmitting immense amounts of information to the brain at any given moment, both from the complex processes related to digestion and also from the input of 100 trillion chattering microbes in our intestinal tracts. In other words, when it comes to collecting, storing, analyzing, and responding to massive amounts of information, the gutbrain axis is a true supercomputer—a far cry from the plodding digestive steam engine it was once thought to be.
This realization is all part of our new, modern understanding of gut function, which includes a shift from a preoccupation with details of macro- and micronutrients, metabolism, and calories to the knowledge that our gut with its nervous system and its microbial residents is actually an amazing information-processing machine that greatly surpasses our brains in terms of the number of cells involved and rivals some of the brain’s capabilities. Through our food supply this system connects us closely to the world around us, picking up vital information about how our food is grown, what we put into our soil, and what chemicals were added to it before we buy it in the supermarket. And as we will learn in greater detail in the following chapter, the gut microbes play a prominent role in this connection between what we eat, and how we feel.