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Gut Thoughts
by Maia Szalavitz
Posted February 1, 2002 · Issue 119
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Abstract
Though few know about it, humans have a second brain that
handles most of the body's digestive functions. Study of the
enteric nervous system is a rapidly growing specialty, offering
insight into malfunctions of the "gut brain" as well as the more
complex cranial brain.
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Digestion is such a prosaic function that most people prefer not
to think about it. Fortunately, they don't have to - at least
not with the brain in their heads. Though few know about it,
humans (and other animals) have a second brain that handles most
digestive functions.
Deep in your gut lies a complex self-contained nervous system
containing more nerve cells than the spinal cord, and indeed
more neurons than all the rest of the peripheral nervous system.
There are over 100 million nerve cells in the human small
intestine alone.
Malfunctions of this "gut brain" may be involved in irritable
bowel syndrome (IBS), a condition that affects an estimated 20
percent of the U.S. population and is believed to be responsible
for $8 billion in health care costs alone in the United States
each year, according to the International Foundation for
Functional Gastrointestinal Disorders. Patients with IBS suffer
bouts of chronic diarrhea, constipation, or sometimes both
alternately. IBS is the most common diagnosis made by
gastroenterologists.
The study of the enteric nervous system is a rapidly growing
specialty known as neurogastroenterology.
"What the gut has to do is extremely complicated," says Michael
Gershon, chair of the department of anatomy and cell biology at
the Columbia University College of Physicians and Surgeons and
author of The Second Brain (Harper Perennial, 1999). "If the
brain had to control that, it would have to run huge cables and
have a huge number of cells devoted solely to that purpose. It
makes great evolutionary sense to [separate these functions] and
essentially use a microcomputer that is independent rather than
a central processing unit."
In fact, researchers believe that the gut brain evolved first -
because digestion came before locomotion in multicellular
creatures. In mammals, the two systems originate near each other
in the outer layer of the early embryo.
Like many poorly understood organs, the gut brain was discovered
by classical anatomists in the 19th century and then ignored.
"No one knew what it did," says David Wingate, emeritus
professor of gastrointestinal science at Queen Mary, University
of London. "When you'd ask what it was for in medical school,
they'd say, 'Let's move on.'"
In 1899, physiologists studying dogs found that unlike any other
reflex, the continuous push of material through the digestive
system (now called the peristaltic reflex) continued when nerves
linking the brain to the intestines were cut.
By the 1970s, a society for the study of gastrointestinal
motility had been set up - but how this motility was controlled
remained unclear. The vagus nerve, for example, sends some
fibers from the brain to the gut; however, it connects directly
with only a tiny minority of cells there.
In 1965, Gershon published a paper in Science suggesting that
serotonin might act as a neurotransmitter in the gut. At the
time, acetylcholine and norepinephrine were accepted as
transmitters in the peripheral nervous system, but serotonin was
seen as a centrally acting transmitter used by some nerves to
modulate the action of others.
The peripheral nervous system wasn't supposed to use such
controls - only the brain and spinal cord were believed to
process information through "interneurons" such as those
containing serotonin.
At a meeting of the Society for Neuroscience in 1981, however,
Gershon and others marshaled enough data to finally convince
skeptics that serotonin was indeed a key transmitter in the gut.
In fact, it is now known that 95% of the body's serotonin is
used by the gut - and the enteric nervous system contains every
neurotransmitter and neuromodulator found so far in the brain.
"We now know quite a lot about the library of programs run by
the [gut brain]," says Jackie Wood, professor of physiology and
cell biology and of internal medicine at Ohio State University.
"For example, when the bowel is empty, one particular program
runs." Called the migrating motor complex (MMC), this involves a
series of movements running from the stomach to the end of the
small intestine, which is believed to function in keeping the
potentially dangerous bacteria stored in the colon from moving
upwards rather than out.
At least 500 different species of deadly bacteria have been
found to inhabit a person's colon at any given time; "traveler's
diarrhea" often results when this mix is changed through
exposure to new pathogens. If this happens, the gut runs a
program designed to expel as much of its contents as quickly as
possible - unpleasant for the vacationer, but much better than a
fatal infection.
"Another program involves a flood of serotonin throughout the
entire circuit, which produces the digestive pattern that mixes
and stirs the contents," says Wood.
Because the gut brain is smaller and more accessible than the
brain itself, understanding it could offer insights about how to
parse the more complex organ. "[That idea] was what lead me to
begin my research when I was a fledgling neuroscientist," says
Gershon. "I looked at the brain and found it daunting, and I
still do, so I looked for a simpler nervous system to study." He
adds, "'Simple nervous system,' of course, turned out to be an
oxymoron."
Unlike the cranial brain, however, the gut brain doesn't seem to
be conscious - or at least, in health, it doesn't impinge much
on consciousness. "The gut is not an organ from which you like
to receive frequent progress reports," says Gershon. For most
digestive processes, no news is good news.
The problem in IBS, in fact, may be that the enteric nervous
system becomes overly sensitive to normal functioning and
reports to the brain when it shouldn't. Or, the brain may
overreact to normal bowel signals.
Normally, the brain may avoid conscious awareness of most gut
activity. But in IBS, says Wingate, one theory is that "the
barrier to information being projected into consciousness is
lowered."
As in many heterogeneous conditions defined by symptoms rather
than specific pathology, different subgroups of patients may
have different causes or varying levels of contributions by
different factors.
In some cases, IBS may be an autoimmune problem - something like
multiple sclerosis of the gut, where immune cells attack nervous
tissue. "If you catch it early enough," says Wood, "You can use
steroids to treat it [in such cases]." High doses of steroids
shut down immune activity and prevent immune cells from causing
harm, but they don't help once damage has been done.
The gut is, in fact, a major immune organ, containing more
immune cells than the rest of the body combined. The enteric
nervous system interacts intimately with the immune system, and
can affect mood and behavior by signaling the central nervous
system.
Further, the gut brain may in fact be the only system that can
refuse central signals. Says Gershon, "The gut brain can say no
to the big brain, absolutely. In fact, there are nerve fibers
that project towards the CNS, and if the [bowel] doesn't like
the message, it can turn it off or cancel it."
Indeed, the vagus nerve mostly carries information from the
enteric nervous system to the brain - for every one message sent
by the brain to the gut, about nine are sent in the other
direction. And recent research has found that stimulating this
nerve can have antidepressant and even learning-enhancing
effects - so "gut feelings" could genuinely be more than just a
metaphor.
The similarities between the two nervous systems may also mean
that they are vulnerable to similar toxins and disease
processes. For example, in both Parkinson's disease and
Alzheimer's, the degenerative processes seen in brain nerve
cells are also seen in the neurons of the enteric system.
This link could also help explain the connection between
psychological problems and gut problems - and could put to rest
the myth that problems such as IBS are simply "neuroses" because
they so often occur in people with other psychological disorders.
It may be that the real reason that bowel disorders often
accompany psychological problems is that both brain and gut
neurons are suffering simultaneously - in addition to the fact
that having to spend a significant portion of one's life
attending to bathroom functions is in itself depressing.
Simultaneous effects of drugs on both systems also account for
the gastrointestinal "side effects" of Prozac and other drugs
that act on serotonin metabolism - which actually may have more
effect on the bowel than on the brain, because serotonin
predominates in the bowel and the drug moves through the
digestive system before reaching the brain.
Fortunately, in most people, the bowel quickly develops
tolerance to these drugs, and gastrointestinal side effects
usually subside within a few days or weeks of the start of
treatment. In fact, low doses of SSRI (selective serotonin
reuptake inhibitor) drugs may actually help patients with IBS.
And since different serotonin receptors predominate in the brain
and in the gut, new drugs may be developed to affect certain
subtypes but not others.
"What's exciting," says Wingate, "is getting away from
essentially anecdotal ways of categorizing patients by symptoms
and being able to study [their problems] in a very systematic
biological way."
Maia Szalavitz is a health/science journalist who has written
for the New York Times, the Washington Post, Newsday, New York
Magazine, Salon, and other major publications.
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