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The gut has a mind of its own

Operating like the cranial brain and looking uncannily
similar to it, the gut brain is continuously active,
whether we're aware of it or no, writes CHANTAL OUIMET

By CHANTAL OUIMET
Special to The Globe and Mail

Tuesday, December 31, 2002 � Page R7

Ever wonder why you get cramps when you're stressed? Or why you get "butterflies" in your stomach before a job interview? And why your gut tells you not to trust a certain person?

Scientists say it's because the body has two brains -- the familiar one encased in our skull and another more obscure one in our gut. This "second brain," known as the enteric nervous system, is located in our digestive tract and holds about 100-million nerve cells -- more than in our spinal cord.

Less complex and smaller than our cranial brain, this "second brain," which contains between 70 to 85 per cent of the body's immune cells, is an independent data-processing centre handling a complicated circuitry of neurons, neuromodulators and neurotransmitters.

"Every neurotransmitter that exists in our brain, also exists in the gut without exception. The brain in the gut is simply the brain gone south," says Dr. Michael Gershon, author of The Second Brain, and chairman of the department of anatomy and cell biology at Columbia University College of Physicians and Surgeons.

In 1899, anatomists and physiologists studying dogs found that, unlike any other reflex, the continuous push of material through the digestive system continued after nerves linking the brain to the intestines were severed. In other words, they discovered the gut had a mind of its own.

Operating like our brain and looking uncannily similar to it, the gut brain responds to stimulus and is continuously active whether we're aware of it or not. But it doesn't think or feel. Feeling is held in the cerebral cortex of the brain. This "second brain" performs a different role.

"The brain in the head deals with the finer things in life: religion, philosophy, appreciation of art and music, creativity, etc.," says Dr. Gershon. "Whereas the brain in the gut deals with this dirty, messy and disgusting business of digestion. The brain in the head doesn't have to get its hands dirty with that kind of thing since it has delegated the job."

They may have different roles but our two brains are interconnected. One thousand to 2,000 nerve fibres connect them and enable the two to talk. When one gets upset, the other one does too.

"I don't think we could have made that statement a few years ago. . . . We've been finding out that the nerves in the gut independently regulate gut function, but do so in a dialogue with the nerves in our head. It's a nerve-to-nerve discussion," says Keith Sharkey, physiology and biophysics professor at the University of Calgary.

Interest in the gut brain resurfaced in the early 1980s after new technology became available.

"For the first time, we were able to see in elegant and exquisite detail the specific way that nerves went from A to B," explains Prof. Sharkey. "That gives you a chance to ask questions that could not or had not been asked before."

There are approximately 250 research laboratories now studying the enteric nervous system around the world. This new breed of neuroscientists is not only fuelling the present renaissance in the field of neurogastroenterology (study of the nerves entrenched in the lining of the esophagus, stomach, small intestine and colon), but offering insights into malfunctions of both brains.

Scientists have discovered that the gut brain may be involved in gastrointestinal disorders like ulcerative colitis, Crohn's disease and irritable bowel syndrome -- a condition that affects between 15 and 20 per cent of the population.

"Back in the days when . . . I was a medical student, I was taught that these diseases were psychosomatic. . . . But they're a real thing. Your gut can literately drive your brain crazy," notes Dr. Gershon. "If you are walking around with a burning sensation in your upper belly and it feels terrible, you can get pretty anxious. Likewise, if you've got aches and you're on the toilet with diarrhea every five minutes, it can change your personality. But it's more than that."

For many years, individuals (mostly women) with irritable bowel syndrome, a functional disorder characterized by abdominal pain, bloating, flatulence, diarrhea and/or constipation, suffered in silence. Doctors believed the illness was imagined -- all in the head.

"We now know IBS is not psychosomatic. There is an element of the brain controlling the gut which has to be born in the mind. But we now understand that there is also an organic and physiological basis for the functional changes in the little brain," declares Prof. Sharkey.

Dr. Nicholas Diamant, a gastroenterologist at Toronto Western Hospital and an emeritus professor of medicine and physiology at the University of Toronto, agrees that both brains are involved in the disorder.

"The brain sends signals down to the little brain via the spinal cord which acts as a gate for the pain signals," Dr. Diamant says. "The brain may not be closing this gate adequately to modulate and regulate the signals coming up from the gut. Therefore, the brain is letting more signals come up than it normally would."

A study by the Mayo Foundation published this August in Gastroenterology, the official journal of the American Gastroenterological Association, suggested there is genetic determinant that predicts the response to medication of IBS patients with diarrhea-predominant symptoms.

"It has to do with how the body inactivates the [neuro]transmitter serotonin. In some patients, the body inactivation is more efficient and the patient therefore responds better to the medication," explains Dr. Michael Carmilleri, professor of medicine and physiology at the Mayo Clinic in Rochester and one of the authors of the report.

"It's a landmark paper. . . . We are starting to relate changes in the signalling in the 'second brain' to real diseases based not only on functional changes but on genetic studies as well," says Prof. Sharkey.

This July, a drug came on the Canadian market to treat patients (women only) with constipation-predominant IBS. Experts say Tegaserod, known commercially as Zelnorm, is only effective in 60 to 65 per cent of people.

"IBS is defined by a series of symptoms," says Prof. Sharkey. "It's a multiple disease entity. . . . We don't understand it well enough to ever consider a miracle-type cure because it's too complicated for that."

In the case of Crohn's disease and ulcerative colitis (both autoimmune diseases), Dr. Carmilleri says the gut brain may play a role. "There is some interaction between the immune cells in the intestines and the 'second brain.' "

The discovery of the brain-gut connection also allowed scientists to learn what is at the heart of the most visceral human emotions. A gut feeling, for example, isn't just a poetic image used to convey intuition. It arises from the interplay between our two brains.

"It's a "body loop" which is activated every time we are being challenged or stressed. From a lifetime of activating this "body loop" during good or bad situations, we learn to interpret this preverbal feedback as good or bad," says Emeran Mayer, professor of medicine and physiology at the University of California -- Los Angeles.

Butterflies are minor indicators of pain and another example of this close relationship. Prof. Mayer says when one is faced with an anxiety-ridden situation, the brain in our skull sends urgent messages to our "second brain" and throws it off balance. "The big brain also becomes more sensitive to signals from the gut and amplifies them to unpleasant conscious sensations," he wrote. Therefore, one reads this response as gurgling or "butterflies" in the belly.

Stomach cramps, heartburn, diarrhea or constipation due to stress are again an illustration of the gut rising to the level of conscious perception. "The dialogue between the brain in our head and the brain in our gut sometimes goes awry. . . . in such a way that the brain in our gut responds inappropriately to stimulus," says Prof. Sharkey. In turn, the nerves tell the muscles to contract more or less or make the glands secrete more or less fluid.

Not all of the signals sent from the "second brain" to the cranial brain are bad news. "Some of the information that is being sent from the gut to the brain can establish how well the brain in the head works. . . . Your gut doesn't think for you but if it's behaving well, it can contribute to your mood being good," says Dr. Gershon. As a result, this interaction plays a role in dictating behavior and in creating human joy as well as sadness.

Scientists affirm the brain constantly communicates and listens to our "second brain." Its functions are then taken over by the brain with respect to the activation of major emotions such as fear, anxiety, anger, sadness or happiness. There is no direct proof but a lot of suggestive evidence.

"Chemicals released from cells within the 'second brain' . . . can activate vagal sensory neurons (cells high in the neck) which signal back to the brain. These vagal sensory neurons play a prominent role in many emotional processes and it is certainly conceivable that such signals play a role in generating happiness or a sense of well-being. The newborn gets its first sense of well-being from stimulation of the gut and release of chemicals through milk," wrote Prof. Mayer.

Dr. Diamant, a specialist in the mind-body connection, says each person's "second brain" reacts differently. "If you think everybody feels the same thing when the gut does something, you are in deep trouble. You have to consider the whole person and all the baggage they carry. The gut's reaction may be based on many experiences as well as the individual's genetic makeup."

It's an exciting time for scientists because research in the field of neurogastroenterology is still evolving. Even medical students are generally shocked by the "second brain's" complexity. "That hasn't really made it to the textbooks yet," says Prof. Sharkey. "It takes a few years for emerging knowledge to become dogma."

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Gut Feelings: The Surprising Link Between Mood and Digestion

Chris Woolston

CONSUMER HEALTH INTERACTIVE

� Listening to your gut
� The stress alarm
� Functional disease in a dysfunctional world
� Setting your mind on relief

If you've ever felt your insides twist in knots before a big speech, you know the stomach listens carefully to the brain. In fact, the entire digestive system is closely tuned to a person's emotions and state of mind, says William E. Whitehead, PhD, a professor of medicine and an adjunct professor of psychology at the University of North Carolina. People with irritable bowel syndrome often suffer flare-ups during times of stress and anxiety, and even perfectly healthy people can worry their way to stomach pain, nausea, diarrhea, constipation, or other problems. Even if a doctor can't find anything physically wrong, the misery is real.

In the past -- back when scientists believed the mind and the body operated as separate entities -- some physicians wrote off digestive distress with no sign of organic disease as being "all in the head." But in recent years, that wall has crumbled. Doctors now see intricate links between the nervous system and the digestive system. The two realms constantly exchange streams of chemical and electrical messages, and anything that affects one is likely to affect the other. The connections between the two systems are so tight that scientists often refer to them as one entity: the brain-gut axis. (The brain-gut axis is a hot topic in medicine. In the summer of 2001, more than 100 researchers from around the world gathered in Los Angeles for a convention called "2001: A Brain-Gut Odyssey.") For people suffering from persistent digestive troubles unconnected to disease, such research suggests that reducing stress, depression, and anxiety may go a long way toward calming the gut.

Listening to your gut
It may surprise many people to learn that the gut actually contains as many neurons (nerve cells) as the spinal cord. In an article in the medical journal Gut, author J. D. Woods and colleagues compare this network -- known as the enteric nervous system, or ENS -- to a "local mini-brain" storing a library of programs for different patterns of gut behavior." Woods and colleagues compare the ENS to a microcomputer with its own independent software, "whereas the brain is like a larger mainframe with extended memory and processing circuits that receive information from and issue commands to the enteric computer."

With all these messages, the connection between the brain and the digestive system is a busy two-way street. The central nervous system releases chemicals (acetylcholine and adrenaline) that tell the stomach when to produce acid, when to churn, and when to rest. Similar signals help guide the movements of the intestines. The digestive system responds by sending electrical messages to the brain, creating such sensations as hunger, fullness, pain, nausea, discomfort, and possibly sadness and joy.

As strange as it sounds, our guts just might help shape our moods, says Emeran Mayer, MD, a gastroenterologist and the chairman of the new Mind-Body Collaborative Research Center at the University of California at Los Angeles. Mayer points to the vagus nerve, essentially a large electrical cable that runs between the brain and the digestive system. "Doctors once believed the nerve's main job was controlling acid production in the stomach," Mayer says. "But 95 percent of the fibers go the other direction -- from the gut to the brain."

Nobody knows exactly what messages travel along this cable, but scientists have found that stimulating the nerve at different frequencies can cause either anxiety or a strong sense of well being. Perhaps the term "gut feeling" isn't just a figure of speech after all.

Mayer suggests another intriguing possibility: Prozac and similar antidepressants may actually work on the gut, not the brain. Drugs known as SSRIs (short for selective serotonin reuptake inhibitors) ease depression by enhancing levels of serotonin. Most experts assume it's the extra serotonin in the brain that helps improve mood. But 95 percent of the serotonin in the body actually lies within the digestive system. Perhaps, Mayer says, SSRIs do their job by boosting serotonin in the gut and changing the signals along the vagus nerve.

The stress alarm
Whatever messages may be passing back and forth, they can easily become garbled in times of stress. When the brain senses a threat, real or imagined, it sounds the alarm by flooding the body with adrenaline and another hormone called CRF (short for corticotropin-releasing factor). These hormones trigger the "fight or flight" response -- helpful back in the days when humans had to run from lions, but a potential liability when we lose a job or go through a divorce.

If you suffer from frequent emotional distress -- perhaps because of extreme stress, depression, or anxiety -- the unrelenting flood of adrenaline and CRF will take a toll on your digestive system. For one thing, the hormones can make the cells in the stomach and intestines extra-sensitive to pain. As a result, normal contractions and movements can become excruciating. The new signals can also disrupt the motion of the intestines, causing bouts of constipation or diarrhea.

Functional disease in a dysfunctional world
Because of the close connection between the brain and many abdominal disorders, a multinational team of investigators, specialists, and federal research agencies convened in the mid-1980s to develop criteria for diagnosing more than 20 digestive disorders known as "Functional Gastrointestinal Disorders," or FGIDs. A "functional" disease, in this case, means a disturbance in GI function that it isn't related to any injury, infection, or other obvious physical problem. These criteria, which include persistent constipation, diarrhea, bloating, abdominal pain, or irritable bowel syndrome unrelated to diagnosable physical disorder, was recently updated by an international team known as the Rome II Committee, which called for a classification system of these disorders based on clusters of common symptoms.

Among the disorders the committee examined is irritable bowel syndrome (IBS), a very common and perplexing malady often characterized by painful cramps, bloating, and constipation alternating with diarrhea. If you have "functional" IBS, you may feel that "dysfunctional" is a much more apt term.

Emotional distress alone can't cause IBS -- the source of the disorder is still unknown -- but stress or a mood disorder may worsen the symptoms. In fact, few other conditions provide such a clear illustration of the link between the mind and the body. One recent Australian study found that chronic distress -- arising from such traumas as divorce, lawsuits, serious illnesses, or job troubles -- accounted for 97 percent of all changes in IBS symptoms. Interestingly, short-term swings in mood don't seem to have much effect on IBS, which explains why many people still suffer symptoms on relatively calm, relaxing days.

In a similar manner, strange messages along the gut-brain axis also seem to be a major cause of "functional" dyspepsia, or indigestion. People with dyspepsia often experience the discomfort of constant ulcer pain without actually having ulcers. Stress definitely makes the symptoms worse, but the effect isn't nearly as dramatic as with irritable bowel syndrome. If adding stress to functional dyspepsia is like throwing woodchips on a fire, combining stress with IBS is like dousing a blaze with gasoline.

The influence of the mind on the gut goes beyond functional diseases. For instance, people with Crohn's disease or ulcerative colitis -- two conditions with clearly physical origins -- often suffer flareups during times of emotional stress. And in a recent survey, 68 percent of people with basically healthy digestive systems said stress gives them stomachaches.

Setting your mind on relief
So what can you do if your mind and your digestive system aren't getting along? One thing you shouldn't do is suffer silently. Ask your doctor if you would be a good candidate for cognitive behavioral therapy, interpersonal therapy, relaxation therapy, or another form of counseling. In several studies, these treatments have been shown to give IBS patients more relief than standard medical therapies. You might even consider hypnosis or self-hypnosis.

While rarely used in the United States, hypnosis is a popular -- and apparently effective -- treatment for IBS in Europe, Whitehead says. Preliminary studies suggest it may also help ease functional dyspepsia.

It's worth noting that Prozac and other SSRIs may help calm the stomach. Small doses of a tricyclic antidepressant -- too small to affect mood -- can lessen stomach pain, presumably by blocking pain messages.

There's another reason to go to the doctor: Simply hearing you're not crazy or gravely ill may be a great source of comfort. "Reassurance from a physician is probably the most effective treatment [for IBS]," Mayer says.

Supportive docs will never go out of style, but even better treatments for IBS and other functional disorders may soon be on the way. Researchers are currently studying medications designed to block the release of CRF, the hormone that helps translate stress into stomach trouble. Mayer says the medication may be available in a little more than a year.

But you don't have to wait that long to get better. Do what you can to avoid stress and work closely with your doctor. With a little luck, your gut feelings will be much more pleasant.

-- Chris Woolston, M.S., is a health and medical writer with a master's degree in biology. He is a contributing editor at Consumer Health Interactive, and was the staff writer at Hippocrates, a magazine for physicians. He has also covered science issues for Time Inc. Health, WebMD, and the Chronicle of Higher Education. His reporting on occupational health earned him an award from the northern California Society of Professional Journalists.

References

D.A. Drossman. The functional gastroinestinal disorders and the Rome II process. Gut, September 1999, Volume 45, Supplement II.

Babette S. Duncan, Pharm.D., Walter "Buzz" Stewart, Ph.D., MPH. Gastrointestinal Disorders. Innovative Medical Research (IMR), AdvancePCS.

Emeran Mayer, telephone interview.

Rome II: A Multinational Consensus Document on Functional Gastrointestinal Disorders. Gut: An International Journal of Gastroenterology and Hepatology. September 1999, No. II, Vol. 45.

UCLA-The Inside TRAK. Does stress cause IBS or similar disorders in other
parts of the GI tract?

J.D. Wood et al. Fundamentals of neurogastroenterology. Gut, September 1999. Volume 45. Supplement II.

William Whitehead, telephone interview.

Wilhelmsen I. The role of psychosocial factors in gastrointestinal
disorders. Gut. December 2000

Wilhelmsen I. Brain-gut axis as an example of the bio-psycho-social model.
Gut.

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Reviewed by George W. Meyer, MD, FACP, a staff gastroenterologist at Kaiser Permanente in Sacramento, Calif.; and John Inadomi, MD, a gastroenterologist and assistant professor of medicine at the University of Michigan Medical Center.

First published August 27, 2001
Last updated July 17, 2003
Copyright � 2001 Consumer Health Interactive

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Heather is the Administrator of the IBS Message Boards. She is the author of Eating for IBS and The First Year: IBS, and the CEO of Heather's Tummy Care. Join her IBS Newsletter. Meet Heather on Facebook!

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