The Enteric Nervous System: The Brain in the Gut
The gut has a mind of its own, the "enteric nervous system". Just like the larger brain in the head, researchers say, this system sends and receives impulses, records experiences and respond to emotions. Its nerve cells are bathed and influenced by the same neurotransmitters. The gut can upset the brain just as the brain can upset the gut.
The gut's brain or the "enteric nervous system" is located in the sheaths of tissue lining the esophagus, stomach, small intestine and colon. Considered a single entity, it is a network of neurons, neurotransmitters and proteins that zap messages between neurons, support cells like those found in the brain proper and a complex circuitry that enables it to act independently, learn, remember and, as the saying goes, produce gut feelings.
The gut's brain is reported to play a major role in human happiness and misery. Many gastrointestinal disorders like colitis and irritable bowel syndrome originate from problems within the gut's brain. Also, it is now known that most ulcers are caused by a bacterium not by hidden anger at one's mother.
Details of how the enteric nervous system mirrors the central nervous system have been emerging in recent years, according to Dr. Michael Gershon, professor of anatomy and cell biology at Columbia-Presbyterian Medical Center in New York. He is one of the founders of a new field of medicine called "neurogastroenterology."
The gut contains 100 million neurons - more than the spinal cord. Major neurotransmitters like serotonin, dopamine, glutamate, norephinephrine and nitric oxide are in the gut. Also two dozen small brain proteins, called neuropeptides are there along with the major cells of the immune system. Enkephalins (a member of the endorphins family) are also in the gut. The gut also is a rich source of benzodiazepines - the family of psychoactive chemicals that includes such ever popular drugs as valium and xanax.
In evolutionary terms, it makes sense that the body has two brains, said Dr. David Wingate, a professor of gastrointestinal science at the University of London and a consultant at Royal London Hospital. "The first nervous systems were in tubular animals that stuck to rocks and waited for food to pass by," according to Dr. Wingate. The limbic system is often referred to as the "reptile brain." "As life evolved, animals needed a more complex brain for finding food and sex and so developed a central nervous system. But the gut's nervous system was too important to put inside the newborn head with long connections going down to the body," says Wingate. Offspring need to eat and digest food at birth. Therefore, nature seems to have preserved the enteric nervous system as an independent circuit inside higher animals. It is only loosely connected to the central nervous system and can mostly function alone, without instructions from topside.
This is indeed the picture seen by developmental biologists. A clump of tissue called the neural crest forms early in embryo genesis. One section turns into the central nervous system. Another piece migrates to become the enteric nervous system. According to Dr. Gershon, it is only later that the two systems are connected via a cable called the vagus nerve.
The brain sends signals to the gut by talking to a small number of "command neurons," which in turn send signals to gut interneurons that carry messages up and down the pike. Both command neurons and interneurons are spread throughout two layers of gut tissue called the "myenteric plexus and the submuscosal plexus." Command neurons control the pattern of activity in the gut. The vagus nerve only alters the volume by changing its rates of firing.
The plexuses also contain glial cells that nourish neurons, mast cells involved in immune responses, and a "blood brain barrier" that keeps harmful substances away from important neurons. They have sensors for sugar, protein, acidity and other chemical factors that might monitor the progress of digestions, determining how the gut mixes and propels its contents.
As light is shed on the circuitry between the two brains, researchers are beginning to understand why people act and feel the way they do. When the central brain encounters a frightening situation, it releases stress hormones that prepare the body to fight or flee. The stomach contains many sensory nerves that are stimulated by this chemical surge - hence the "butterflies." On the battlefield, the higher brain tells the gut brain to shut down. A frightened running animal does not stop to defecate, according to Dr. Gershon.
Fear also causes the vagus nerve to "turn up the volume" on serotonin circuits in the gut. Thus over stimulated, the gut goes into higher gear and diarrhea results. Similarly, people sometimes "choke" with emotion. When nerves in the esophagus are highly stimulated, people have trouble swallowing.
Even the so-called "Maalox moment" of advertising can be explained by the interaction of the two brains, according to Dr. Jackie D. Wood, chairman of the department of physiology at Ohio State University in Columbus, Ohio. Stress signals from the head's brain can alter nerve function between the stomach and esophagus, resulting in heartburn.
In cases of extreme stress, Dr. Wood say that the higher brain seems to protect the gut by sending signals to immunological mast cells in the plexus. The mast cells secrete histamine, prostaglandin and other agents that help produce inflammation. This is protective. By inflaming the gut, the brain is priming the gut for surveillance. If the barrier breaks then the gut is ready to do repairs. Unfortunately, the chemicals that get released also cause diarrhea and cramping.
There also is an interaction between the gut brain and drugs. According to Dr. Gershon, "when you make a drug to have psychic effects on the brain, it's very likely to have an effect on the gut that you didn't think about." He also believes that some drugs developed for the brain could have uses in the gut. For example, the gut is loaded with the neurotransmitter serotonin. According to Gershon, when pressure receptors in the gut's lining are stimulated, serotonin is released and starts the reflexive motion of peristalsis. A quarter of the people taking Prozac or similar antidepressants have gastrointestinal problems like nausea, diarrhea and constipation. These drugs act on serotonin, preventing its uptake by target cells so that it remains more abundant in the central nervous system.
Gershon also is conducting a study of the side effects of Prozac on the gut. Prozac in small doses can treat chronic constipation. Prozac in larger doses can cause constipation - where the colon actually freezes up. Moreover, because Prozac stimulates sensory nerves, it also can cause nausea.
Some antibiotics like erythromycin act on gut receptors to produce ascillations. People experience cramps and nausea. Drugs like morphine and heroin attach to the gut's opiate receptors, producing constipation. Both brains can be addicted to opiates.
Victims of Alzheimer's and Parkinson's diseases suffer from constipation. The nerves in their gut are as sick as the nerve cells in their brains. Just as the central brain affects the gut, the gut's brain can talk back to the head. Most of the gut sensations that enter conscious awareness are negative things like pain and bloatedness.
The question has been raised: Why does the human gut contain receptors for benzodiazepine, a drug that relieves anxiety? This suggests that the body produces its own internal source of the drug. According to Dr. Anthony Basile, a neurochemist in the Neuroscience Laboratory at the National Institutes of Health in Bethesda, MD, an Italian scientist made a startling discovery. Patients with liver failure fall into a deep coma. The coma can be reversed, in minutes, by giving the patient a drug that blocks benzodiazepine. When the liver fails, substances usually broken down by the liver get to the brain. Some are bad, like ammonia and mercaptan, which are "smelly compounds that skunks spray on you," says Dr. Basile. But a series of compounds are also identical to benzodiazepine. "We don't know if they come from the gut itself, from bacteria in the gut or from food, but when the liver fails, the gut's benzodiazepine goes straight to the brain, knocking the patient unconscious, says Dr. Basile.
The payoff for exploring gut and head brain interactions is enormous, according to Dr. Wood. Many people are allergic to certain foods like shellfish. This is because mast cells in the gut mysteriously become sensitized to antigens in the food. The next time the antigen shows up in the gut, the mast cells call up a program, releasing chemical modulators that try to eliminate the threat. The allergic person gets diarrhea and cramps.
Many autoimmune diseases like Krohn's disease and ulcerative colitis may involve the gut's brain, according to Dr. Wood. The consequences can be horrible, as in "Chagas disease," which is caused by a parasite found in South America. Those infected develop an autoimmune response to neurons in their gut. Their immune systems slowly destroy their own gut neurons. When enough neurons die, the intestines literally explode.
A big question remains. Can the gut's brain learn? Does it "think" for itself? Dr. Gershon tells a story about an old Army sergeant, a male nurse in charge of a group of paraplegics. With their lower spinal cords destroyed, the patients would get impacted. "At 10am every morning, the patients got enemas. Then the sergeant was rotated off the ward. His replacement decided to give enemas only after compactions occurred. But at 10 the next morning everyone on the ward had a bowel movement at the same time, without enemas." Had the sergeant trained those colons?
The human gut has long been seen as a repository of good and bad feelings. Perhaps emotional states from the head's brain are mirrored in the gut's brain, where they are felt by those who pay attention to them.
Reference: Taken from "A contemporary view of selected subjects from the pages of The New York Times, January 23, 1996. Printed in Themes of the Times: General Psychology, Fall 1996. Distributed Exclusively by Prentice-Hall Publishing Company.
Here are comments and further explanation to the above report from Steve Flatt, Director of the Psychological Therapies Group in Liverpool, England:
Dear Dr King,
I came across your site somewhat by accident and read the material on the enteric nervous system and have to take issue with one statement in the piece which I will follow up elsewhere as well. Gershon suggests that animals do not stop to defecate when running in fear. Actually they do and frequently. It is used as a masking technique to confuse the predator! Watch any lion hunt on zebra and you will see in action. Furthermore observation of many humans in feared situationsand their sphincters open and release the contents of bowels and bladder. Indeed it isso well known that film director use a close up of a spreading stain to increase tension and highlight fear in their films. Also people who are very scared, projectile vomit as another defence against attack by predators. Many people report the desire to throw up during feared situations and come to fear the symptoms themselves (of restricted throat, clenching stomach, etc.) these are all primitive responses aimed at increasing survival.
Steve Flatt, Director
The Psychological Therapies Unit
24 Rodney Street
Tel: 0151 709 2112
Mobile: 07970 610 377
Download Article on the Gut's Bacterial System Here:
Gut Reaction: The Vibrant Ecosystem Inide the Human Gut Does More than Digest Food, by Sarah C.P. Williams, Howard Huges Medical Institute Bulletin, 14-17, August 2010.