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    Gut Thoughts

    by Maia Szalavitz
    Posted February 1, 2002 · Issue 119


    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.

    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

    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

    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

    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

    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

    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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