Gut: The Inside Story of Our Body's Most Underrated Organ (Revised Edition)

by Giulia Enders

  The Three-Day Rule

  MANY DOCTORS PRESCRIBE laxatives without explaining the three-day rule, although it is easy to remember and is a useful aid. The large intestine has three sections: the ascending, transverse, and descending colon. When we go to the toilet, we usually empty the last section. By the next day, it has filled up again and the game starts all over again. Taking a strong laxative may cause the entire large intestine—all three sections—to be emptied. It can then easily take three days before the large intestine is full again.

  1. Normal situation: one-third of the large intestine is emptied and it is full again by the next day.

  2. After taking a laxative: the entire large intestine is emptied and it may take three days to fill up again.

  Those unfamiliar with the three-day rule will likely start to get nervous during that time. Still no bowel movement? And before they know it, they’ve taken the next laxative tablet or powder. This is a vicious and unnecessary circle. After taking a laxative, the gut deserves a couple of days’ respite. Monitoring for normal bowel movements should begin on the third day. Slow transporters may need to give a helping hand to their gut after two days.

  The Brain and the Gut

  THIS IS A sea squirt.

  It may be enlightening to learn the sea squirt’s view on the necessity of having a brain. The sea squirt, like humans, is a member of the chordate phylum. It has a bit of a brain and a kind of spinal cord. The brain blithely sends messages to the rest of the body via the spinal cord and receives interesting information in return. In humans, for example, it might receive an image of a traffic sign from the eyes; a sea squirt’s eyes might tell it when a fish swims by. A human’s brain might receive information from the sensors in the skin about whether it’s cold outside; a sea squirt’s skin sensors can tell its brain about the temperature of the water deeper in the sea. A human might get information about whether certain foods are good to eat . . . and so might a sea squirt.

  Equipped with all this information, a young sea squirt navigates the great oceans until it finds a rock that is secure, located in water that is just the right temperature, and surrounded by food. Having found a home, the sea squirt settles down. Sea squirts are sessile animals: once they take up residence, they never move again, no matter what happens. The first thing a sea squirt does after setting up home is to eat its own brain. And why not? It’s possible to live and be a sea squirt without one.

  Daniel Wolpert is not only an engineer and medical doctor who has won many academic honors, he is also a scientist who believes the sea squirt’s attitude to having a brain is very significant. His theory is that the only reason for having a brain is to enable movement. On first hearing, that might sound like an annoyingly mundane statement. But perhaps we just consider the wrong things mundane.

  Movement is the most extraordinary thing ever developed by living creatures. There is no other reason for having muscles, no other reason for having nerves in those muscles, and probably no other reason for having a brain. Everything that has ever been done in the history of humankind was only possible because we are able to move. Movement is not just walking or throwing a ball. It is also pulling faces, uttering words, and putting plans into action. Our brain coordinates its senses and creates experience in order to produce movement: movement of the mouth or the hands, movement over many miles or over just a few inches. Sometimes, we can also influence the world around us by suppressing movement. But if you’re a tree and can’t choose whether you move or not, you don’t need a brain.

  The common or garden sea squirt no longer needs a brain after it has settled in one place. Its time of movement is over, and so its brain is surplus to requirements. Thinking without moving is less useful than having a mouth opening to eat plankton with. The latter influences the balance of nature at least a tiny bit.

  We humans are very proud of our particularly complex brains. Thinking about constitutional law, philosophy, physics, or religion is an impressive feat and can prompt extremely sophisticated movements. It is awe-inspiring that our brains are capable of all this. But at some point, that awe wears off, and we hold our brains responsible for everything we experience in life—we think up experiences of well-being, happiness, or satisfaction inside our own heads. When we are insecure, anxious, or depressed, we worry that the computer in our heads might be broken. Philosophizing and physics research are matters of the mind and always will be—but there is more to our self than that.

  And it is from the gut that we learn this lesson—the organ that is responsible for little brown heaps and unbidden sounds and smells of all sorts. This is the organ that is currently forcing researchers to rethink. Scientists are cautiously beginning to question the view that the brain is the sole and absolute ruler over the body. The gut not only possesses an unimaginable number of nerves, those nerves are also unimaginably different from those of the rest of the body. The gut commands an entire fleet of signaling substances, nerve-insulation materials, and ways of connecting. There is only one other organ in the body that can compete with the gut for diversity—the brain. The gut’s network of nerves is called the “gut brain” because it is just as large and chemically complex as the gray matter in our heads. Were the gut solely responsible for transporting food and producing the occasional burp, such a sophisticated nervous system would be an odd waste of energy. Nobody would create such a neural network just to enable us to break wind. There must be more to it than that.

  We humans have known since time immemorial something that science is only now discovering: our gut feeling is responsible in no small measure for how we feel. We are “scared shitless” or we can be “shitting ourselves” with fear. If we don’t manage to complete a job, we can’t get our “ass in gear.” We “swallow” our disappointment and need time to “digest” a defeat. A nasty comment leaves a “bad taste in our mouth.” When we fall in love, we get “butterflies in our stomach.” Our self is created in our head and our gut—no longer just in language, but increasingly also in the lab.

  How the Gut Influences the Brain

  WHEN SCIENTISTS STUDY feelings, they start out by looking for something to measure. They draw up scales for suicidal tendencies, test hormone levels to measure love, or set up trials for tablets to treat anxiety. To outsiders, this often appears less than romantic. In Frankfurt, there was even a study that involved scanning the brains of volunteers while a research assistant tickled their genitals with a toothbrush. Such experiments tell scientists which areas of the brain receive signals from which parts of the body. This helps them draw a map of the brain.

  So they now know, for example, that signals from the genitals are sent to the upper central part of the brain, just below the crown. Fear is found in the middle of the brain—right between the ears, so to speak. Word formation is located just above the temple. Morality is located behind the forehead, and so on. In order to improve our understanding of the relationship between the gut and the brain, we must trace their communication pathways. How do signals get from belly to brain, and what effect do they have when they get there?

  Signals from the gut can reach different parts of the brain, but they can’t reach everywhere. For example, they never end up in the visual cortex at the back of the brain. If they did, we would see visual effects or images of what is going on in our gut. Regions they can end up in, however, include the insula, the limbic system, the prefrontal cortex, the amygdala, the hippocampus, and the anterior cingulate cortex. Any neuroscientists reading this will be up in arms when I roughly define the responsibilities of these brain regions as, respectively, self-awareness, emotion, morality, fear, memory, and motivation. This does not mean that our guts control our moral thinking, but it allows for the possibility that the gut might have a certain influence on it. Scientists need to conduct more laboratory experiments to look more closely at that possibility.

  The forced swimming test, carried out on mice, is one of the most revealing experiments performed in the name of research into motivati
on and depression. A mouse is placed in a small container of water that is too deep for it to reach the bottom with its feet, forcing it to swim around trying in vain to get to dry land. The question is, how long will it keep swimming in pursuit of its aim? This boils down to one of the basic questions of our existence: how intensely are we prepared to strive for something that we believe exists? That might be something concrete, like dry land beneath our feet or high school graduation. Or it might be something abstract, like satisfaction or happiness.

  Areas of the brain activated by vision, fear, word formation, moral thought, and genital stimulation.

  Mice with depressive tendencies do not swim for long. They simply freeze, apathetically awaiting their fate. It seems inhibitory signals are transmitted more efficiently in their brains than motivational or driving impulses. Such mice also show a stronger reaction to stress. New antidepressants can normally be tested on these mice. If they swim for longer after receiving the medication, it is an indication that the substance under scrutiny might be effective.

  Researchers in the team, led by the Irish scientist John Cryan, took this one step further. They fed half their mice with Lactobacillus rhamnosus (JB-1), a strain of bacteria known to be good for the gut. Back in 2011, the idea of altering the behavior of mice by changing the contents of their gut was very new. And, indeed, the mice with the enhanced gut flora not only kept swimming for longer and with more motivation, but their blood was also found to contain fewer stress hormones. Furthermore, these mice performed better in memory and learning tests than their unenhanced peers. When scientists severed their vagus nerve, however, no difference was recorded between the two groups of mice.

  The vagus nerve is the fastest and most important route from the gut to the brain. It runs through the diaphragm, between the lungs and the heart, up along the esophagus, through the neck to the brain. Experiments on humans have shown that people can be made to feel comfortable or anxious by stimulating their vagus nerve at different frequencies. In 2010, the European Union approved a medical treatment that uses stimulation of the vagus nerve to help patients suffering from depressive disorders. So, this nerve works something like a telephone connection to the switchboard at a company’s headquarters, transferring messages from staff out in the field.

  The brain needs this information to form a picture of how the body is doing. This is because the brain is more heavily insulated and protected than any other organ in the body. It nestles in a bony skull, surrounded by a thick membrane, and every drop of blood is filtered before it is allowed to flow through the regions of the brain. The gut, by contrast, is right in the thick of it. It knows all the molecules in the last meal we ate, inquisitively intercepts hormones as they swim around in the blood, inquires of immune cells what kind of day they’re having, and listens attentively to the hum of the bacteria in the gut. It is able to tell the brain things about us it would never otherwise have had an inkling of.

  The gut has not only a remarkable system of nerves to gather all this information, but also a huge surface area. That makes it the body’s largest sensory organ. Eyes, ears, nose, or the skin pale by comparison. The information they gather is received by the conscious mind and used to formulate a response to our environment. They can be seen as life’s parking sensors. The gut, by contrast, is a huge matrix, sensing our inner life and working on the subconscious mind.

  Cooperation between the gut and the brain begins very early in life. Together, they are responsible for a large proportion of our emotional world when we are babies. We love the pleasant feeling of a full stomach, get terribly upset when we are hungry, or grizzle and moan with wind. Familiar people feed, change, and burp us. It’s palpably clear that our infant self consists of the gut and the brain. As we get older, we increasingly experience the world through our senses. We no longer scream blue murder when we don’t like the food at a restaurant. But the connection between gut and brain does not disappear overnight, it simply becomes more refined. A gut that does not feel good might now subtly affect our mood, and a healthy, well-nourished gut can discreetly improve our sense of well-being.

  The first study of the effect of intestinal care on healthy human brains was published in 2013—two years after the study on mice. The researchers assumed there would be no visible effect in humans. The results they came up with were surprising not only for them, but for the entire research community. After four weeks of taking a cocktail of certain bacteria, some of the areas of the subjects’ brains were unmistakably altered, especially the areas responsible for processing emotions and pain.

  Of Irritated Bowels,

  Stress, and Depression

  NOT EVERY UNCHEWED pea can intervene in the brain’s activity. A healthy gut does not transmit minor, unimportant digestive signals to the brain via the vagus nerve. Rather, it processes them with its own brain—that’s why it has one, after all. If it thinks something is important, however, it may consider calling in the brain.

  By the same token, the brain does not transfer every piece of information to the conscious mind. If the vagus nerve wants to deliver information to the extremely important locations in the brain, it must get them past the doorman, so to speak. The brain’s bouncer is the thalamus. When our eyes report to the thalamus for the twentieth time that the same curtains are still hanging at the living-room window, it refuses entry to that information—it is not important for the conscious mind. A report of new living-room curtains is something it would let in, for example. That is not true of everybody’s thalamus, but most people’s.

  An unchewed pea will not make it across the threshold from the gut to the brain. The story is different for other stimuli, however. For example, a report of an unusually large intake of alcohol will make it from the belly to the head, where it informs the vomit control center; information about trapped gas will reach the pain center; and the presence of pathogenic substances will be reported to the officer in charge of nausea. These stimuli make it through because the gut’s threshold and the brain’s doorman consider them important. But it is not only bad news that makes it across the border. Some signals can cause us to fall asleep on the couch, contented and full after a big Christmas dinner. We are conscious that some of these signals originate from the belly; others are processed in the subconscious areas of the brain and so cannot be located so clearly.

  When a gut is irritated, its connection to the brain can make life extremely unpleasant. This shows up on brain scans. In one experiment, the activity in the brains of volunteers was imaged while a small balloon was inflated inside their intestine. Healthy subjects showed normal brain activity with no notable emotional components. When patients with irritable bowels were subjected to the same procedure, however, there were clear indications of activity in the emotional center of the brain normally associated with unpleasant feelings. So the stimulus was able to cross both barriers in those subjects. The patients felt uneasy, although they had not endured anything untoward.

  Irritable bowel syndrome is often characterized by an unpleasant bloated feeling or gurgling in the abdomen, and a susceptibility to diarrhea or constipation. Sufferers also have an above-average incidence of anxiety or depressive disorders. Experiments like the one with the balloon show that feeling unwell and negative emotions can arise via the gut–brain axis when the gut’s threshold is lowered or when the brain insists on having information it would not normally receive.

  Such a state of affairs may be caused by tiny but persistent (so-called micro-) inflammations, bad gut flora, or undetected food intolerances. Despite the wealth of recent research, some doctors still dismiss patients with irritable bowel syndrome as hypochondriacs or malingerers because their tests show no visible damage to the gut.

  Other diseases affecting the bowel are different. During an acute phase of their condition, patients with a chronic inflammatory bowel disease like Crohn’s disease or ulcerative colitis may have real sores in their bowel wall. With these conditions the trouble is not that even tiny stimuli a
re transferred from the gut to the brain—their threshold is still high enough to prevent that. The problems are caused by the diseased mucus membrane of the gut. Like patients with irritable bowel syndrome, sufferers of these conditions also show increased rates of depression and anxiety.

  There are currently very few—but very good—research teams studying how to make the threshold between the gut and the brain less porous. This is important not only for patients with intestinal problems, but for all of us. Stress is thought to be among the most important stimuli discussed by the brain and the gut. When the brain senses a major problem (such as time pressure or anger), it naturally wants to solve it. To do so, it needs energy, which it borrows mainly from the gut. The gut is informed of the emergency situation via the sympathetic nerve fibers, and is instructed to obey the brain in this exceptional period. It is kind enough to save energy on digestion, producing less mucus and reducing the blood supply.

  However, this system is not designed for long-term use. If the brain permanently thinks it is in an emergency situation, it begins to take undue advantage of the gut’s compliance. When that happens, the gut is forced to send unpleasant signals to the brain to say it is no longer willing to be exploited. This negative stimulus can cause fatigue, loss of appetite, general malaise, or diarrhea. As with emotional vomiting in response to upsetting situations, the gut reacts by ridding itself of food to save energy so it is available to the brain. The difference is that real stress situations can continue for much longer than minor upsets. If the gut has to continue to forego energy in favor of the brain, its health will eventually suffer. A reduced blood supply and a thinner protective layer of mucus weaken the gut walls. The immune cells that dwell in the gut wall begin to secrete large amounts of signal substances, which make the gut brain increasingly sensitive and lower the first threshold. Periods of stress mean the brain borrows energy, and, as any housekeeper knows, good budgeting is always better than running up too many debts.