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"The gut can work independently of any control by the brain in
your headit's functioning as a second brain," says Michael Gershon,
professor and chair of pathology and cell biology at Columbia.
"It's another independent center of integrative neural
activity."
After five decades of groundbreaking work leading to discovery
of the gut's brainknown technically as the enteric nervous system
(ENS)Gershon reassured me that he, too, still feels the twisting of
his own intestines under periods of high stress, especially
whenever he calls the National Institutes of Health to find out
where he stands on his newest research grant applications. "I
become painfully aware of the kind of signals the gut can send to
the brain," he confides.
That anguish has paid off. With an astonishing 100 million
neuronsmore than in the spinal cord but a lot fewer than in the
brainarrayed over an intricately folded surface area more than a
hundred times greater than that of your skin, he has found, the ENS
can work all on its own, without any input from the brain, to
control the movement and absorption of food throughout the
intestines. No other organ can call its own tune without the baton
of that conductor who stands on the pedestal above the neck.
Your Backup BrainThere's a "second brain" in your stomach. It
influences your mood, what you eat, the kinds of diseases you get,
as well as the decisions you make. And you thought it was all in
your head!By Dan Hurley, published on November 01, 2011 - last
reviewed on May 24, 2012
There is, you may be happy to know, a guru of intestinal
intelligence. And as improbable as it sounds, he just may be able
to explain why you get depressed and anxious, dive for the peanut
butter when you are stressed, and rely on "gut instincts," among
many other matters of the mind. Meeting him turned out to be a
gut-wrenching experienceliterally. When a security guard at
Columbia University's College of Physicians and Surgeons kept me
waiting 45 minutes in the lobby while checking and rechecking my
credentials, my stomach began churning like a washing machine. By
the time the guard let me upstairs, I had one question for the
researcher regarded as the father of the new field known as
neurogastroenterology: Was the pain in my stomach all in my
head?
The answer turned out to be double-sided. You see, it depends on
which brain you wish to talk about: the one in your head or the
other one, in your gut.
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"The nervous system actually started out in the gut," says
Emeran Mayer, director of the UCLA Center for Neuro-visceral
Sciences and Women's Health as well as of the UCLA Center for
Neurobiology of Strest of my patients have a very good
understanding that there is a close connection between their
emotions and their guts. But there are still very few
neuroscientists who understand the complexity of this enteric
nervous system and its links to the brain."
As he explained in a recent article in the journal Nature,
creatures low on the evolutionary totem pole, such as helminths, a
class of worms, have a single nervous system that is very much like
our own ENS. "The ganglia that form the primitive brains of
helminths, and eventually the brains of higher mammals, were
derived from the more primitive but homologous enteric nervous
circuits. Neural circuitries and transmitter systems that have
evolved to assure optimal responses to the challenges presented in
our internal environment may have been incorporated into the
central nervous system during evolution."
It is only logical that the gut should have a nexus of sensors
to gather vital information. After all, like the brain in our head,
it is engaged in prolonged contact and interaction with the outside
worldin this case, via the food we swallow.
But the ENS, the newest mind-body connection to be revealedand
sometimes considered a branch of the autonomic nervous system,
although Gershon sees it as holding its owndoes much more than
control itself. It also sends signals north to the brain that
directly affect feelings of sadness or stress, even influence
memory, learning, and decision-making. It relies on, and in many
cases manufactures, more than 30 neurotransmitters, including
serotonin, that are identical to those in the brain. What's more,
tinkering with the second brain in our gut has lately been shown to
be a potent tool for achieving relief from major depression. Even
autism, studies suggest, may be wrapped up in the neurobiology of
the brain down under.
And it must accomplish an extraordinary feat of transformation.
It is the job of the gut to take in an extensive array of external
matter, break it down to its component parts, shuttle it off to
various internal organs, and turn it into us.
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Think of yourself as the biological equivalent of a doughnut,
with the inner lining of your intestines, the doughnut hole, facing
an "inner" external worldfood, water, bacteria, and whatever else
you swallowjust as your skin faces the "outer" external world.
While your ears, eyes, and sense of touch permit you to see, hear,
and feel the outer exterior of your body, the intestines employ the
ENS to sense, manipulate, and respond to the inner exterior, the
doughnut hole of your gut.
From humans all the way down to such primitive sea creatures as
the lamprey eel and the hagfish, all vertebrates have an ENS in
addition to a central nervous system (CNS). During gestation, in
the first days after conception, precursor cells destined to become
neurons in the gut aggregate in a transitory structure in the
developing embryo called the neural crest. From there they migrate
to the just-formed gut, where they grow into the network of neurons
lining the intestine.
When, 50 years ago, as a fledgling physician, Gershon decided to
study the ENS, only one other researcher in the world focused on
it. Today there are hundreds, and they are all at the cutting edge
of science. In 1998 Gershon published the manifesto of this new
science, The Second Brain. In laying the foundation for much
current research, it alsomost improbablyled to a 2007 appearance by
Gershon on The Colbert Report. "My guest, Dr. Michael Gershon,
believes we have a second brain in the gut. I'll ask him where he
thinks the first one is," Colbert deadpanned.
That Mac 'n' Cheese Feeling
"We all know that food can affect mood and emotions," says
Giovanni Cizza, chief of the Section on Neuroendocrinology of
Obesity at the National Institute of Diabetes and Digestive and
Kidney Diseases. We all recognize that great class of edibles known
as comfort food. But until recently, there had never been a
scientific demonstration of how food affects feelings, how it
brings comfort. The conventional wisdom holds that the succor
provided by foods like chocolate or macaroni and cheese is purely
psychological, based simply on our seeing the food and remembering
Mom's cooking. A competing view is that it is based on the
delicious taste or smell of the food. But neither view turns out to
be correct.
In fact, specific components of the food exert a direct effect
on neurohormones in the gut that then signal the brain, Belgian
researchers have found. They enlisted healthy, normal-weight human
volunteers who agreed to bypass all the pleasurable aspects of
eating by having a nasogastric tube deliver nutrients directly to
their stomachwhile they underwent brain scanning. Through the tube,
volunteers received either an ordinary saline solution or an
infusion of fatty acids. At the same time, they listened either to
neutral music or to melancholy music proven to induce sad feelings,
or they were shown pictures of sad or neutral faces.
The researchers regard the findings as prime proof that the
brain processing of bodily signals regulates emotions. "It's an
important demonstration that in a nonconscious way, without knowing
whether you are getting the fat or the saltwater, something you put
in your stomach can change your mood," Cizza explains. With
apologies to Mom's cooking, not to mention McDonald's, fat, all by
itself, in the absence of any pleasant associations or free toys,
has the power to lift our emotional state.Based on feelings
subjects reported and on brain images the investigators observed,
the fatty acids reduced both sad feelings and sensations of hunger
by about half, compared with the saline. They also reduced feelings
of hunger. Within minutes after the fatty acids hit the stomach,
MRI scans showed that brain regions known to moderate emotions
were
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Illustration by Guyco
activated, with higher levels of blood flow in the brain stem
and most of the emotional parts of the brain, the limbic system.
Fatty-acid infusion attenuated both the behavioral and neural
responses to sad emotion induction, the researchers recently
reported in The Journal of Clinical Investigation.
A recent study by American scientists, published in the same
issue of the journal, illuminated how food influences mood and
behavior. The investigators subjected mice to the equivalent of
schoolyard bullying, exposing them to bigger, older, highly
dominant critters who literally walked all over them. The emotional
effect of such bullying is well established. Animals experience
"chronic social defeat stress," and it is a model of the kind of
prolonged psychosocial stress that in humans can be caused by abuse
or traumaor by being a picked-upon nerd like Peter Parker before he
became Spider-Man. Not only is the experience traumatic, but it is
known to give rise to psychological depression.
Previous studies had established that stressed-out mice go for
high-fat, energy-dense foods. They prefer peanut butter to regular
chow and gain more weight than their low-stress counterparts. The
new study showed that the gut actually tells the brain what to look
for in the larder when the going gets toughwhich is why the mac 'n'
cheese looks better than an
apple at that moment.
It does this by turning on production of ghrelin, a hormone
manufactured by the gut that stimulates hunger in the first brain.
Ghrelin boosts the appeal of food in general, and it specifically
ups the reward value of high-fat foods, probably by turning on
dopamine pathways.
In their studies, the researchers created a mutant strain of
mice stripped of brain receptors for ghrelin. The mutant mice ate
no more high-fat food than did the low-stress mice. A penchant for
peanut butter returned, however, in another strain of mice, ones
that had ghrelin receptors only in regions of
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the brain associated with eating. Ghrelin is but one of many
neurochemical messengers that traffic back and forth between the
ENS and CNS to affect mood and feeding.
"The French have a phrase for it: L'apptit vient en mangeant,"
says Gary J. Schwartz, professor of neuroscience and endocrinology
at Albert Einstein College of Medicine in New York. So do the
Italians: L'appetito viene mangiando. "It means the appetite comes
in the eating. And it's absolutely true: The mere taste of
something fatty is enough to promote further food intake."
Not by Neurohormones Alone
Powerful as they are, neurohormones are not the only players in
the gut-brain axis. There's growing evidence that its activities
are mediated by another key agentthe estimated 100 trillion
bacteria that live inside your intestines and apparently do much
more than digest your food and make you fart.
The vast mass of gut bacteriacollectively known as the gut
biomehas co-evolved over millions of years to live in symbiotic
harmony with us. Most of the bacteria are beneficial. Often called
probiotics, they function as auxiliary DNA, producing their own
enzymes and other products that help process our food and sustain
us. In fact, because of the functional importance of the gut biome
to us, the Human Genome Project has added as one of its goals the
doping out of the genetic makeup of this basic biological
accessory.
"The gut biome is actually an interface between your diet and
your genetics," says Canadian neuroscientist Jane Foster. The human
diet powerfully influences the makeup of the gut flora, and the gut
flora in turn influence our makeup. "Our genetics determines our
predispositions, but the gut biome influences how those
predispositions function on a day-to-day basis," adds Foster,
associate professor of psychiatry and behavioral neurosciences at
Ontario's McMaster University.
Foster and her colleagues have found that from birth on, there
is constant cross talk between gut bacteria and the brain. During
infancy, that communication plays a significant role in shaping how
the brain is wired. It affects not only anxiety but also memory,
creating changes in both the amygdala, the brain's central
regulator of fear, and the hippocampus, the region deep in the
brain that is essential for memory and learning.
"The cross talk between the gut biome and the brain is
continual," says Foster. "That's the important take-home message.
These are not two separate systems; they are two parts of a single
system."
While you can just imagine the jokes yet to come, scientists now
see the bowel as a new pathway for regulating behavior. In
commentary accompanying Foster's report in the journal
Neurogastroenterology and Motility, researchers declared,
"Modulation of the enteric microbiota may be a useful strategy" for
treating stress-related disorders, including depression, and for
helping control such conditions as irritable bowel syndrome and
inflammatory bowel disease.
Is Kimchi the New Prozac?
Studies are already under way to determine which gut flora do
what for our mental health and to turn those findings into
treatments. At the Alimentary Pharmabiotic Centre at University
College Cork in Ireland, John Cryan is working with a strain of
lactobacillus, a common and generally safe bacterium found in the
gut.
Lactobacillus is also a component of yogurt and cheese, as well
as of many fermented foods, including sauerkraut and kimchi. In the
long history of the human species before the advent of
refrigeration, fermented foods played a significant role in our
diet. Now, if they are consumed at all, they
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are occasional condiments, typically added in minuscule amounts.
Cryan has found that the specific lactobacillus strain he is
working with alters the expression of brain-cell receptors for a
key neurotransmitter, GABA, and reduces anxious behaviors in
mice.
"The possibility that distinct patterns of gut flora have an
influence on aspects of our emotional processing is intriguing,"
says UCLA's Emeran Mayer. Although he is cautious about
interpreting the latest findings, he is among the first to bring
rigorous scientific scrutiny to the cognitive effects of probiotics
in humans.
"We're just writing up the results of a study in 40 patients,"
he confides. "But it's going to be pretty revolutionary. Half took
a placebo, and half took a probiotic for three weeks. We took a
brain scan before and after. We were surprised to find that we
could indeed detect a change in brain function in those who took
the probiotic compared to those who received the placebo."
As for probiotic products already on the market, no one has yet
proved scientifically that any of them affect mental or physical
well-being. So far, it seems to be a case of very specific strains
of bacteria having very specific effects.
But it is also possible that changes in the American diet over
the past century have shifted the composition of the gut flora in
ways that render us susceptible to such physical ailments as
diabetes, irritable bowel disease, and immune disorders and to such
mental conditions as depression and anxiety. The incidence of these
conditions has skyrocketed as our diet has turned more to highly
processed foods devoid of the kinds of bacteria our bodies and
brains have unwittingly relied on for eons.
The Autism Connection
Autism has long been linked with disorders of the gut, most
commonly chronic constipation, abdominal pain, and encopresis. In
January 2010, Gershon coauthored a consensus report for the
American Academy of Pediatrics on the gastrointestinal ills that
are often seen in people with
autism spectrum disorders.
"The take-home message is that autism is a genetic disease, and
there are small abnormalities, probably in the synapses, that
affect both the central nervous system and the enteric nervous
system," he says. "People with autism have trouble with both
systems."
Why that is remains a mystery. Perhaps, says Gershon, the
autistic brain causes disorders in the gut. Or it may be that
abnormalities in the gut somehow trigger autism in the brain or
worsen its symptoms. Some parents and researchers believe that a
diet free of gluten and the milk protein casein lessens the
symptoms of autism, although evidence from randomized trials is
limited. Gershon suspects that some combination of genes and
environment causes both the autism and the GI troubles. Despite
much searching, however, so far no study has conclusively
established which way the causal arrow travels.
The ENS Versus the CNS
Researchers are also now unraveling the neurobiology of gut
feelings, those intuitions on which so many of us base personal and
professional decisions. They actually originate not in the gut but
in the brain, when a decision is in the offing. A sensation of
"butterflies" in the stomach arises because the brain sends a
message of anxiety to the gut, which sends messages back to the
brain that it is unhappy.
What to do with that exchange of information? It's best not to
overrely on it. As much as he respects the powers of the ENS,
Gershon does not believe the second brain is conscious or that it
has the capacity for complex emotions or reasoning. "Sometimes
emotions trigger a primitive response
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and the gut contracts a little bit," says Gershon. "It adds an
exclamation point that you notice. That might help you decide
something, but the gut as far as we know is not doing any
reasoning. Religion and philosophy and poetry are for the brain in
the head." Better to use that gut feeling to review the situation
with the first brain.
Although he only tested skin, he believes signals emanating from
the gut, too, can provide useful clues to the brain when we face
tough choices. "I would agree that the ENS helps us to make
decisions," he says.French neuroscientist Wim De Neys recently
found that when people "intuitively" guess wrongly on questions of
logic, their skin gets sweaty, suggesting that they actually
realize an answer is wrong. "The presence of a clear autonomic
conflict response during reasoning lends credence to the idea that
reasoners have a gut feeling signaling that their intuitive
response is not logically warranted," says De Neys.
Decision-making may be firmly monopolized by the executive
center of the brain located above the neck. But that doesn't
minimize the contributions to our mental life now being discovered
in our gut. Unfortunately, the gut's reputation fails to rise to
the occasion. "The gut is a reptilian, disgusting organ, and we're
told to forget about it," Gershon says. "The head is a serious
organ; the heart is a serious organ."
But, like Rodney Dangerfield, the gut may finally be getting
some respect.
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