Fw: A brain in the head, and one in the gut
- A brain in the head, and one in the gut
By Harriet Brown The New York Times
THURSDAY, AUGUST 25, 2005
Two brains are better than one. At least that is the rationale
for the close - sometimes too close - relationship between the
human body's two brains, the one at the top of the spinal cord
and the hidden but powerful brain in the gut known as the
enteric nervous system.
For Dr. Michael Gershon, the author of "The Second Brain" and
the chairman of the department of anatomy and cell biology at
Columbia University, the connection between the two can be
"Every time I call the National Institutes of Health to check on
a grant proposal," Gershon said, "I become painfully aware of
the influence the brain has on the gut."
In fact, anyone who has ever felt butterflies in the stomach
before giving a speech, a gut feeling that flies in the face of
fact or a bout of intestinal urgency the night before an
examination has experienced the actions of the dual nervous
The connection between the brains lies at the heart of many
woes, physical and psychiatric. Ailments like anxiety,
depression, irritable bowel syndrome, ulcers and Parkinson's
disease manifest symptoms at the brain and the gut level.
"The majority of patients with anxiety and depression will also
have alterations of their GI function," said Dr. Emeran Mayer,
professor of medicine, physiology and psychiatry at the
University of California, Los Angeles.
A study in 1902 showed changes in the movement of food through
the gastrointestinal tract in cats confronted by growling dogs.
One system's symptoms - and cures - may affect the other.
Antidepressants, for example, cause gastric distress in up to a
quarter of the people who take them. Butterflies in the stomach
are caused by a surge of stress hormones released by the body in
a "fight or flight" situation. Stress can also overstimulate
nerves in the esophagus, causing a feeling of choking.
Gershon, who coined the term "second brain" in 1996, is one of a
number of researchers who are studying brain-gut connections in
the relatively new field of neurogastroenterology. New
understandings of the way the second brain works, and the
interactions between the two, are helping to treat disorders
like constipation, ulcers and Hirschsprung's disease.
The role of the enteric nervous system is to manage every aspect
of digestion, from the esophagus to the stomach, small intestine
and colon. The second brain, or little brain, accomplishes all
that with the same tools as the big brain, a sophisticated
nearly self-contained network of neural circuitry,
neurotransmitters and proteins.
The independence is a function of the enteric nervous system's
"Rather than Mother Nature's trying to pack 100 million neurons
someplace in the brain or spinal cord and then sending long
connections to the GI tract, the circuitry is right next to the
systems that require control," said Jackie Wood, professor of
physiology, cell biology and internal medicine at Ohio State.
Two brains may seem like the stuff of science fiction, but they
make literal and evolutionary sense.
"What brains do is control behavior," Wood said. "The brain in
your gut has stored within its neural networks a variety of
behavioral programs, like a library. The digestive state
determines which program your gut calls up from its library and
When someone skips lunch, the gut is more or less silent. Eat a
pastrami sandwich, and contractions all along the small
intestines mix the food with enzymes and move it toward the
lining for absorption to begin. If the pastrami is rotten,
reverse contractions will force it - and everything else in the
gut - into the stomach and back out through the esophagus at
In each situation, the gut must assess conditions, decide on a
course of action and initiate a reflex.
"The gut monitors pressure," Gershon said. "It monitors the
progress of digestion. It detects nutrients, and it measures
acid and salts. It's a little chemical lab."
The enteric system does all this on its own, with little help
from the central nervous system.
By the early '80s, scientists had accepted the idea of the
enteric nervous system and the role of neurotransmitters like
serotonin in the gut.
It is no surprise that there is a direct relationship between
emotional stress and physical distress. "Clinicians are finally
acknowledging that a lot of dysfunction in GI disorders involves
changes in the central nervous system," said Gary Mawe, a
professor of anatomy and neurobiology at the University of
The big question is which comes first, physiology or psychology?
The enteric and central nervous systems use the same hardware,
as it were, to run two very different programs. Serotonin, for
instance, is crucial to feelings of well-being. Hence the
success of the antidepressants known as SSRIs that raise the
level of serotonin available to the brain.
But 95 percent of the body's serotonin is housed in the gut,
where it acts as a neurotransmitter and a signaling mechanism.
The digestive process begins when a specialized cell, an
enterochromaffin, squirts serotonin into the wall of the gut,
which has at least seven types of serotonin receptors. The
receptors, in turn, communicate with nerve cells to start
digestive enzymes flowing or to start things moving through the
Serotonin also acts as a go-between, keeping the brain in the
skull up to date with what is happening in the brain below. Such
communication is mostly one way, with 90 percent traveling from
the gut to the head.
Many of those messages are unpleasant, and serotonin is involved
in sending them. Chemotherapy drugs like doxorubicin, which is
used to treat breast cancer, cause serotonin to be released in
the gut, leading to nausea and vomiting. "The gut is not an
organ from which you wish to receive frequent progress reports,"
Serotonin is also implicated in one of the most debilitating gut
disorders, irritable bowel syndrome, or IBS, which causes
abdominal pain and cramping, bloating and, in some patients,
alternating diarrhea and constipation.
"You can run any test you want on people with IBS, and their GI
tracts look essentially normal," Mawe said. The default
assumption has been that the syndrome is a psychosomatic
But it turns out that irritable bowel syndrome, like depression,
is at least in part a function of changes in the serotonin
system. In this case, it is too much serotonin rather than too
In a healthy person, after serotonin is released into the gut
and initiates an intestinal reflex, it is whisked out of the
bowel by a molecule known as the serotonin transporter, or SERT,
found in the cells that line the gut wall.
People with irritable bowel syndrome do not have enough SERT, so
they wind up with too much serotonin floating around, causing
The excess serotonin then overwhelms the receptors in the gut,
shutting them down and causing constipation.
When Gershon, whose work has been supported by Novartis, studied
mice without SERT, he found that they developed a condition very
much like IBS in humans.
Several new serotonin-based drugs - intestinal antidepressants,
in a way - have brought hope for those with chronic gut
Still, psychology clearly plays a role. Recent studies suggest
that stress, especially early in life, can cause chronic GI
diseases, at least in animals. "If you put a rat on top of a
little platform surrounded by water, which is very stressful for
a rat, it develops the equivalent of diarrhea," Mayer said.
Another experiment showed that when young rats were separated
from their mothers, the layer of cells that line the gut, the
same barrier that is strengthened by mast cells during stress,
weakened and became more permeable, allowing bacteria from the
intestine to pass through the bowel walls and stimulate immune
"In rats, it's an adaptive response," Mayer said. "If they're
born into a stressful, hostile environment, nature programs them
to be more vigilant and stress-responsive in their future life."
He said up to 70 percent of the patients he treats for chronic
gut disorders had experienced early childhood traumas like
parents' divorces, chronic illnesses or parents' deaths. "I
think that what happens in early life, along with an
individual's genetic background, programs how a person will
respond to stress for the rest of his or her life," he said.
Either way, what is good for one brain is often good for the
other, too. A team of researchers from Penn State University
recently discovered a possible new direction in treating
intestinal disorders, biofeedback for the brain in the gut.
In an experiment published in a recent issue of
Neurogastroenterology and Motility, Robert Stern, a professor of
psychology at Penn State, found that biofeedback helped people
consciously increase and enhance their gastrointestinal
activity. They used the brains in their heads, in other words,
to help the brains in their guts, proving that at least some of
the time two brains really are better than one.
Ian Pitchford PhD CBiol MIBiol