By Michael Spector, The New Yorker, October 22, 2012
Michael Spector |
Helicobacter
pylori may be the most successful pathogen in human history. While not as
deadly as the bacteria that cause tuberculosis, cholera, and the plague, it
infects more people than all the others combined. H. pylori, which
migrated out of Africa along with our ancestors, has been intertwined with our
species for at least two hundred thousand years. Although the bacterium
occupies half the stomachs on earth, its role in our lives was never clear.
Then, in 1982, to the astonishment of the medical world, two scientists, Barry
Marshall and J. Robin Warren, discovered that H. pylori is the
principal cause of gastritis and peptic ulcers; it has since been associated
with an increased risk of stomach cancer as well. Until that discovery, for
which the men shared a Nobel Prize, in 2005, stress, not an infection, was
assumed to be the major cause of peptic ulcers.
H.
pylori is shaped like a corkscrew and is three microns long. (A grain of
sand is about three hundred microns.) It is also one of the rare microbes that
live comfortably in the brutally acidic surroundings of the stomach. Doctors
realized that antibiotics could rid the body of the bacterium and cure the
disease; treating ulcers this way has been so successful that there have been
periodic discussions of trying to eradicate H. pylori altogether. The
consensus was clear; as one prominent gastroenterologist wrote in 1997, “The
only good Helicobacter pylori is a dead Helicobacter pylori.”
Eradication proved complicated and expensive, however, and the effort never
gained momentum. Yet few scientists questioned the goal. “Helicobacter was
a cause of cancer and of ulcers,’’ Martin J. Blaser, the chairman of the
Department of Medicine and a professor of microbiology at the New York
University School of Medicine, told me recently. “It was bad for us. So the
idea was to get it out of our bodies, as fast as we can. I don’t know of anyone
who said, Gee, we better think about the consequences.”
No
one was more eager to rout the organism from the human gut than Blaser, who has
devoted most of his working life to the study of H. pylori. His laboratory
at N.Y.U. developed the first standard blood tests to identify the microbe, and
most of them are commonly in use today. But Blaser, a restless intellect who,
in addition to his medical duties, helped start the Bellevue Literary
Review, wondered how an organism as old as humans could survive if it caused
nothing but harm. “That isn’t how evolution works,” he said. “H. pylori is
an ancestral component of humanity.” By the nineteen-nineties, Blaser had begun
to look more closely at the bacterium’s molecular behavior, and in 1998 he
published a paper in the British Medical Journal suggesting, contrary
to prevailing views, that it might not be so dangerous after all. The following
year, he started the Foundation for Bacteriology, to help focus attention on
the critical, and usually positive, role that these organisms play in human
evolution.
“We
have a certain narrative,’’ he said, sitting in his laboratory. A Tennessee
license plate—“hpylori”—rested on his desk and a detailed map of the bacterium’s
genome was hanging on a wall. Blaser, wearing a crisp blue sports coat, and
with well-tended gray hair, projects an air of genial confidence; he seems more
like the chief executive of a conglomerate than like the bench scientist he has
been for decades. “Germs make us sick,” he said. “But everyone focusses on the
harm. And it’s not that simple, because without most of these organisms we
could never survive.’’
Since
1953, when James Watson and Francis Crick described the structure of DNA, we
have looked upon genes as our biological destiny. The double helix provided a
blueprint for life, and the process of making a human, while staggeringly
complex, was also straightforward: genes manufacture proteins, which, in turn,
build the various parts we need. When DNA is damaged or genes interact poorly with
one another, the eventual result is disease. To understand how and when our
genes malfunction, then, would be to understand how to prevent, treat, and cure
everything from cancer to the common cold. That search became the central task
of molecular biology. In the past decade, however, aided by the rapidly
escalating power of computer processing and by the same revolution in
DNA-sequencing technology that made it possible to map our genome, another
truth has emerged: while our health is certainly influenced by genes, it may be
affected even more powerfully by bacteria.
We
inherit every one of our genes, but we leave the womb without a single microbe.
As we pass through our mother’s birth canal, we begin to attract entire
colonies of bacteria. By the time a child can crawl, he has been blanketed by
an enormous, unseen cloud of microorganisms—a hundred trillion or more. They
are bacteria, mostly, but also viruses and fungi (including a variety of
yeasts), and they come at us from all directions: other people, food,
furniture, clothing, cars, buildings, trees, pets, even the air we breathe.
They congregate in our digestive systems and our mouths, fill the space between
our teeth, cover our skin, and line our throats. We are inhabited by as many as
ten thousand bacterial species; these cells outnumber those which we consider
our own by ten to one, and weigh, all told, about three pounds—the same as our
brain. Together, they are referred to as our microbiome—and they play such a
crucial role in our lives that scientists like Blaser have begun to reconsider
what it means to be human.
“I
love genetics,” Blaser said. “But the model that places our genes at the root
of all human development is wrong. By itself, it simply cannot explain how
rapidly the incidence of many diseases has risen.” He stressed that genes
matter immensely, but that one must take into account more than just the
twenty-three thousand genes we inherit from our parents. The passengers in our
microbiome contain at least four million genes, and they work constantly on our
behalf: they manufacture vitamins and patrol our guts to prevent infections;
they help to form and bolster our immune systems, and digest food. Recent
research suggests that bacteria may even alter our brain chemistry, thus affecting
our moods and behavior. The process of learning about our microbiome is in its
early days, but even the most tentative results have begun to transform our
understanding of human health. Recently, a group at the University of
Maryland School of Medicine identified twenty-six bacterial species that reside
in the guts of members of the Old Order Amish sect—a closed population, with a
nearly identical gene pool—that seem to account for common metabolic
abnormalities such as high blood pressure and insulin resistance. Similar
research has suggested that the destruction of bacteria may contribute to Crohn’s
disease, obesity, asthma, and many other chronic illnesses. “The prospects here
are endless,’’ Blaser said. “We need to be careful with the science and not
oversell it. But I have been a practicing physician and medical researcher for
more than thirty years, and this is the most exciting and important work of my
lifetime.”
Bacteria
have inhabited the earth for at least two and a half billion years. Our evolutionary
ancestors arrived in a world dominated by microbes, and, as we evolved, so did
they. Until recently, it was nearly impossible to sift through molecules and
determine the impact that those organisms have had on us. Scientists first
needed to locate a microbe in the body, then remove a sample and grow it in
culture. With billions of cells to examine, the data could never be complete or
even representative. DNA-sequencing technology changed that, opening the
microbial world for the first time to sophisticated scrutiny. After the
successful conclusion of the Human Genome Project, the National Institutes of
Health launched a similar enterprise, in 2007, to map the human microbiome. For
the past five years, scientists associated with the Human Microbiome Project
have followed two hundred and forty-two healthy people, periodically sampling
bacteria from their mouths, nasal passages, skin, and other sites on and in
their bodies. In 2008, the European Commission and China joined the hunt, with
the Metagenomics of the Human Intestinal Tract Project, known as Metahit.
Computers
have made it possible for researchers to purify the DNA contained in thousands
of samples and to separate bacterial from human genes. (Scientists know how to
identify human DNA; when they discard it, genes from the microbiome remain.)
The initial results, published this summer, opened a surprising window on the
human body, detailing the vast range of microbes that colonize nearly every
surface we have. Most reside within the gut, but many also occupy our mouths,
and one particular bacterium, Streptococcus mutans, has been recognized as
the principal cause of tooth decay. When you eat sugar, S. mutans releases
acid that corrodes the teeth. Many researchers who study the microbiome
now look upon cavities as an infectious disease, and they are testing a
mouthwash that kills S. mutans; if it works, dental cavities could
vanish. Microbial communities vary widely within and among people, yet
they are also specific; the microbes found in your mouth, for instance, are far
more likely to resemble the bacteria in another person’s mouth than the
bacteria found in any other part of your body. But our microbial world is
enormous, and it changes constantly: a recent study of a hundred and
twenty-four people in Denmark and Spain found at least a thousand different
species of gut microbes, although each person carried, on average, only a hundred
and sixty species.
All
animals have biomes. There is a cat microbiome, a dog microbiome, an alligator
microbiome, and a dolphin microbiome. Earlier this summer, scientists in North
Carolina State University’s Department of Poultry Science received a grant from
the U.S. Department of Agriculture to study the chicken microbiome. Plants,
too, need microbial communities to survive. Rhizobium, a bacterium that lives
in nodules on the roots of legumes, helps its hosts carry out a series of
chemical steps required to supply much of the earth’s nitrogen. “Like
fifteenth-century explorers describing the outline of a new continent, Human
Microbiome Project researchers employed a new technological strategy to define,
for the first time, the normal microbial makeup of the human body,” Francis
Collins, the director of the N.I.H., said when the project’s initial results
were released, this summer. He called it a remarkable reference database that
would lay “the foundation for accelerating infectious-disease research previously
impossible without this community resource.”
The
Human Microbiome Project has helped scientists identify many species and learn
which parts of our bodies they colonize. But to understand what goes wrong when
we are sick the researchers will need to determine how these organisms interact
with one another and with us. Hardly a week goes by without a new symposium, a
call for a special issue of a scientific publication, or the announcement of a
grant intended to decipher the role of bacteria in any number of diseases. “We
are in that beautiful, euphoric, heady early period,’’ David A. Relman, a
professor of medicine, microbiology, and immunology at the Stanford University
School of Medicine, said. Relman was the first to sequence the genomes of a human
bacterial community—which happened to come from his own mouth. “We see
this in any kind of newly emerging science. I keep trying to inject a bit of
moderation, while not wanting to dampen the enthusiasm of a truly exciting
time. So far, though, there are relatively few circumstances where you can meet
a patient who is benefitting from this.” Relman argues that our biome is a
complex and dynamic network, but one that, despite its importance, remains
poorly understood. “We have to stop looking at medicine as a war between
invading pathogens and our bodies,’’ he told me when we met at his office, at
the V. A. hospital in Palo Alto, where he is chief of infectious diseases. “This
sort of stewardship has more in common with park management than it does with our
current practice of trying, in the broadest way possible, to kill microbes.”
Looked
upon this way, the human body turns out to be a vast, highly mutable ecosystem—each
of us seems more like a farm than like an individual assembled from a rulebook
of genetic instructions. Medicine becomes a matter of cultivation, as if our
bacterial cells were crops in a field. When that community is disturbed, either
by the presence of an excess of bacteria like S. mutans, which causes
cavities, or, more often, through the use of a powerful, broad-spectrum
antibiotic, trouble can arise. Earlier this year, a team led by Susan Lynch, an
associate professor of medicine at the University of California at San
Francisco, reported that the bacteriumLactobacillus sakei may be singularly
capable of warding off the painful sinusitis suffered each year by thirty
million Americans; the incidence of sinusitis is far lower among people who
retain that particular microbe, which is destroyed by antibiotics. In August,
Ilseung Cho, of the New York University School of Medicine, published a study
showing that antibiotics eradicated bacteria, commonly found in the digestive
system of mice, that help the animals metabolize calories efficiently; without
the microbes, the mice absorbed more calories from the same amount of food and
rapidly became obese.
Anyone
with a vegetable garden knows that herbicides will make quick work of your
weeds; but, used the wrong way, they will do the same thing to your food.
Antibiotics, it has become clear, are herbicides for humans. Medically, they
are absolutely vital—but they also can alter our internal ecosystem in ways,
both big and small, that even a decade ago seemed unimaginable.
Ridding
our bodies of nasty microorganisms has been a goal of medicine at least since
the invention of the microscope. The introduction of antibiotics, the signature
medical achievement of the twentieth century, helped solidify that idea. Drugs
such as penicillin and streptomycin have saved millions of lives, and we have
come to see the world as a place filled with germs that ought to be destroyed.
Germophobia is big business in the United States: the market for antibacterial
products—sanitizers, cleansing gels, cutting boards, and cotton swabs—grows
larger every year. Even Disney offers its own brand of hand wipes, and so do
the Yankees.
The
impact is hard to dispute. An American born in 1930 could expect to die by the
age of sixty; currently, the life expectancy of an infant is nearly
seventy-nine years. There are many reasons for that remarkably rapid leap in
longevity: the defeat of infectious diseases such as smallpox and polio; better
standards of nutrition; readily available clean water; and, most important,
perhaps, antibiotics. By the age of eighteen, the average American child has
received from ten to twenty courses of antibiotics. Forty-three million courses
were dispensed in 2010 alone, and throughout the developed world children
receive, on average, at least one such treatment every other year. “Those drugs
have saved countless lives, and it is very important that we not lose sight of
that fact,’’ Blaser said. “Whenever they are used, though, there is collateral
damage. And we are only now fully learning how severe that damage has been.”
At
the beginning of the twentieth century, H. pylori occupied the
stomach of nearly every person in the world. Although it remains prevalent in
developing countries, where sanitation is often poor and antibiotic use less
common, it is found in just five per cent of children born in the United States—a
dramatic change echoed in many other Western countries. The relationship
between H. pylori and disease has been well documented, but people
rarely develop ulcers and stomach cancer early in life. During the past fifteen
years, however, Blaser and a growing group of colleagues have shown that H.
pylori performs beneficial functions that begin in infancy. In doing so,
they have transformed the vanishing bacterium into a cautionary symbol of what
can happen when we tinker with the ecological communities inside us. “This is
just the best understood example,’’ Blaser told me. H. pylori is a
complicated resident in our gut, and a reminder that the microbiome is dynamic,
its constituents and effects changing over time. For some people, particularly
as they age, H. pylori poses a serious threat. But in most cases it
is commensal, the term scientists use to describe organisms that benefit from
living on their hosts—us, in this case—without adverse effect. “There are
specific circumstances under which Helicobacter can cause harm,’’
Blaser said, “but without it we are in real trouble.”
He
pointed to asthma rates, which have risen rapidly in the developed world since
the end of the Second World War, when antibiotics became widely available. The
growth seems to have been matched by an equally sharp decline in the percentage
of children infected with H. pylori. Coincidences like that are not rare
in biology. (Causes and correlations are frequently confused. Vaccines have
been mistakenly blamed for autism, for instance, because the condition often
becomes apparent at about the time most children receive their largest cluster
of vaccines. Nonetheless, no relationship between the two has ever been
demonstrated.) Blaser conducted a larger and more targeted study. In 2007,
after analyzing the Third National Health and Nutrition Examination Survey, in
which more than seventy-five hundred adults participated, Blaser and his N.Y.U.
colleague Yu Chen reported that people who didn’t have H. pylori in
their guts were far more likely to have had asthma as children than those who
did.
Last
year, Anne Müller, at the Institute of Molecular Cancer Research, at the
University of Zurich, went further. She infected half of a cohort of mice with H.
pylori, then exposed both
groups
to dust mites and to other, more severe allergens, in an effort to induce the
cellular inflammation that is a hallmark of asthma. In every case, the mice
without the bacterium became ill and those that carried it did
There is
equally convincing evidence that destroying H. pylori could alter
metabolism in ways that increase the risk of obesity. Several research groups,
including Blaser’s, have found a strong relationship in humans between the
bacterium and two stomach hormones, ghrelin and leptin, both of which play
central roles in regulating our appetites. Like many hormones, they work as a
team, telling us to eat when we are hungry and stop when we are full. The more
ghrelin you have in your bloodstream, the more likely you are to overeat.
Leptin functions in the opposite way, suppressing the appetite and increasing
energy levels. For people whose stomachs are infected with H. pylori, ghrelin
became far less detectable after a meal. For the others, levels of the hormone
remained high, and the effects are evident. “A generation of kids are growing
up without H. pylori regulating their levels of ghrelin,’’ Blaser
told me. These results suggest that the message to stop eating never makes it
to the brain. If those hormones aren’t controlled, it becomes far more
difficult to control one’s weight.
A
team from Blaser’s lab then fed antibiotics to mice in dosages that were
comparable to those used to treat children with ear infections. The diet of the
mice remained unchanged, but, compared with a control group, they gained
considerable weight. That finding was not a complete surprise. Roughly
three-quarters of the antibiotics consumed in the United States are fed to
poultry, cows, and pigs, not to treat illness but as dietary supplements to
promote faster growth. That saves the meat industry a lot of money; the
sooner the animals reach a market weight, the sooner they can be slaughtered
and sold. Until recently, the biochemical reasons for that weight gain, and its
unsettling implications for humans, were murky. The new data suggest that even
minimal exposure to antibiotics alters the gut bacteria of these animals, which
may influence their ability to metabolize nutrients properly. As a result,
researchers have concluded, both their body-fat percentage and their weight
increase significantly.
In
2009, Blaser joined with the Stan ford microbiologist Stanley Falkow to write
an essay titled “What Are the Consequences of the Disappearing Human
Microbiota?,” which was published in the journal Nature Reviews
Microbiology. It has been cited often, largely because the two provided a
compelling answer to their own question. For the past hundred and fifty million
years, nearly all mammals have acquired their microbiome by passing through
their mother’s vagina, which is colonized by an enormous range of bacterial
species. Babies delivered by Cesarean section lack many microbes that are
routinely transferred from mother to child. Last year, nearly a third of the
four million children born in the United States were delivered by Cesarean
section. (In China, the figure was closer to fifty per cent.) The incidence of
allergies and asthma is far higher among those children than it is for
vaginal-birth babies. Moreover, this loss of microbial diversity appears to be
cumulative. “The way we live now, we are losing these organisms, and each
generation arrives with fewer than the one before,’’ Blaser said.He took the
theoretical case of a woman who was born at the turn of the twentieth century
and possessed ten thousand species of bacteria. Beginning in the
nineteen-thirties, with the advent of antibiotics, most people began to have
one or two courses of antibiotics in their lives. After the war, hygiene
improved as well. The result: fewer bacterial species in our microbiome. “Let’s
say that the woman is down to nine thousand nine hundred and fifty,’’ he went
on. “And then she has a daughter. That child is likely to take many more
antibiotics than her mother did. She starts life with fewer species and she
will lose more as she goes along.’’ Project this trend forward a few
generations, and the implications are worrisome. “A lot of things are happening
at once,’’ he said. “The rise in obesity, celiac disease, asthma, allergy
syndromes, and Type 1 diabetes. Bad eating habits are not sufficient to explain
the worldwide explosion in obesity.’’
Blaser
walked me through the warren of his lab, where more than a dozen students,
scholars, postdocs, and colleagues from Japan, Mexico, and Sweden, among other
countries, were working on this problem. We stared at computer screens filled
with detailed pictures of mice so enormous they looked like floats in the Macy’s
Thanksgiving Day Parade; they had all been fed steady, low doses of
antibiotics. “We are not talking about illnesses that are increasing by ten per
cent,’’ Blaser said. “They are doubling and tripling and quadrupling. With each
generation, there is a heavier impact on the early-life microbiome. And it
means we are less and less able to metabolize the food we eat.”
Andrew
Goldberg, who is the director of rhinology and sinus surgery at the U.C.S.F.
Medical Center, likes to tell a story about earwax. One day in 1986, when he
had just begun a residency at the University of Pittsburgh School of Medicine,
a man walked into the clinic. The patient had been there many times before,
always for the same reason—a chronic infection in his left ear. Stubborn
ailments like that are common, though they usually occur in both ears.
“It
was one of those refractory cases,” Goldberg told me recently. “The doctors had
tried everything: several types of antibiotics, antifungal drops, the works.
That was standard practice, and we were proud of ourselves for doing it.”
Goldberg and I sat one chilly August afternoon in a coffee shop across from his
office, in the Clinical Sciences Building. He spoke almost wistfully, as if
recalling an antiquated practice, like bloodletting. Despite repeated
treatments, the man’s ear had not improved. But on this day he walked into the
clinic with a smile, and Goldberg soon saw why: the ear looked great. “I have
not felt this well in years,’’ the patient said. “Do you want to know what I
did?” The doctor assumed that one of the drugs had finally found its mark. “I
took some wax out of my good ear and put it into my bad ear, and in a few days
I was fine,” the patient said.“
I
thought he was nuts,’’ Goldberg told me. He never gave the encounter another
thought—until a couple of years ago, when he began to investigate the causes of
those common ear infections. Goldberg explained that earwax contains many
bacterial species and that antibiotics might have destroyed one or more in his
bad ear. “It was actually something like a eureka moment,’’ he said, chuckling.
“I realized that this patient was the perfect experiment: a good ear and a bad
ear separated by a head. That guy wasn’t crazy; he was right. Clearly, he had
something protecting one ear that he then transferred to the other ear. Drugs
didn’t cure him. He cured himself.”
Goldberg
worries about the modern reliance on antibiotics. “We have always had this
scorched-earth policy,” he continued. One of his research specialties is
chronic sinusitis, which is the fifth most common reason people take
antibiotics. “The annual economic burden is more than two billion dollars,” he
said. Goldberg and his associates at U.C.S.F. have found that the sinus
passages of a person with sinusitis are typically inhabited by some nine
hundred strains of bacteria. Remarkably, a healthy person has even more—twelve
hundred species. “Our contention is that other elements of the bacterial
community are keeping the infection in check,” Goldberg said. “Those microbes
are the equivalent of the good earwax. And for eighty years we have done
everything in our power to get rid of all of them.”
It’s
going to take time, and much more research, before bacteria are used as if they
were drugs. But for clinicians like Katherine Lemon the future can’t arrive
soon enough. Lemon is a microbiologist on the staff of the Forsyth
Institute, in Cambridge; an infectious-disease specialist at Boston Children’s
Hospital; and an assistant professor of pediatrics at Harvard Medical School.
Along with Michael Fischbach, an assistant professor in the Department of
Bioengineering and Therapeutic Sciences at U.C.S.F., and others, Lemon is
trying to understand why bacteria infect some people but not others. One of her
projects revolves around a curious fact: thirty per cent of Americans are
vulnerable to a wide range of infections, it appears, because Staphylococcus
aureus bacteria colonize in their nostrils. But seventy per cent don’t
harbor that microbe; Lemon is trying to discover how the good bacteria manage
to keep the staph out.
“One
of these days—not tomorrow, but I hope not in the distant future—we will sample
the microbiome of every child the first time his parents bring him to the
doctor,” Lemon said. Lemon, who is forty-seven, has a square face and graying
hair that constantly seems to fall into her eyes. We were talking in her office
at Forsyth, which was founded more than a century ago as a dental clinic for
underprivileged children. It has since expanded its focus. “We will do what we
do now: take blood, administer vaccines, run the usual tests,” she said. “But
we will have this invaluable extra tool of being able to understand how
children’s microbial communities develop.
“And
I can envision a conversation with the parents,’’ she went on, “where the
pediatrician would say, ‘Your child’s blood work is fine. She is hitting all
her milestones and she looks great. But after seeing her gut microbiome, given
the history of inflammatory-bowel disease in your family, I would like to
prescribe a probiotic that can help populate her intestines with the proper
combination of microbes.’ ” In order to do that, of course, Lemon and other
scientists will have to agree upon what a healthy microbiome looks like. Since
the bacteria in our bodies change throughout our lives, the task will not be
simple.
Last
year, however, researchers led by Peer Bork, of the European Molecular Biology
Laboratory, in Heidelberg, discovered that people can be classified by the type
of bacterial species that dominate their guts. The group found that humans fall
into one of three categories—called enterotypes—none of which correlate to age,
race, or gender. The finding, analogous to the discovery, a century ago, that
there are four blood types, could eventually help lead to treatments. “Some
things are pretty obvious already,’’ Bork told the Times when the
research was published. “Doctors might be able to tailor diets or drug
prescriptions to suit people’s enterotypes.” He added that, instead of
prescribing antibiotics, a doctor might, on the basis of these categories,
restore bacteria that had been destroyed. As many as forty per cent of children
treated with a broad-spectrum antibiotic will develop a condition called
pediatric antibiotic-associated diarrhea. Several clinical trials have now
indicated that the use of probiotics during antibiotic treatment might prevent
this disease.
“It’s
early work but very promising,’’ Lemon told me. “And there is even more hopeful
research in other areas.” About ten per cent of people carry a bacterium called Clostridium
difficile. The bacterium is normally held in check by other residents of the
gut. But when those companion bacteria are destroyed by antibiotics C.
difficile can erupt, causing severe diarrhea and deadly inflammation in
the colon. Nearly every C. difficile infection occurs as a result of
antibiotic treatment, and the incidence has risen sharply in the U.S. in the
past twenty years. The infection causes tens of thousands of deaths in the
world, and hundreds of thousands of illnesses among hospital patients. Most
patients recover; many need several additional courses of antibiotics. For
some, the destruction of their microbiome has been so severe that no treatment
seems to work. “Those patients suffer terribly,’’ Lemon told me. “They are in
agony and, really, there has been nothing to do but try to treat their
condition every time it returns.’’
Recently,
out of desperation as much as anything else, researchers have resorted to what
seems like an extreme treatment: fecal transplants. Doctors obtain fecal
bacteria from healthy donors—normally family members—and place them in the
patient’s intestines, usually during a colonoscopy. There have been only a few
brief trials, but the results have been astounding. In one study, all
thirty-four recipients were cured; these are people for whom all other
approaches had failed. Other trials have reported success rates of more than
eighty per cent. “There are obviously other diseases that could be susceptible
to this kind of microbial therapy,’’ Lemon said; she mentioned
inflammatory-bowel disease, allergies, and recurring ear infections. The hope
is that someday researchers will treat bacteria with highly specific
antibiotics and then rebuild our damaged ecosystem with probiotics—strains of
bacteria that could act as surrogate farmers in our internal ecosystems. One
study, in mice, showed that the toxic side effects of a colon-cancer drug were
eased by blocking a particular bacterial enzyme. “It’s promising,’’ Lemon told
me. “But we need to move very carefully to confirm the results when they look
so good.”
Late
one night, while flipping through television channels, I came upon an
advertisement for a probiotic called Culturelle. After a tag line, “Bacteria Is
Beautiful,’’ the ad featured satisfied customers who testified to the “awesome”
relief they obtained from diarrhea, constipation, and other digestive ailments.
This, the manufacturer suggested, is because Culturelle offers “Lactobacillus
GG, the good bacteria,” which has been “clinically shown to improve your
digestive health.”
The
promise of microbiome research rests largely on the future of probiotics, but
so far such treatments have been more useful as experimental tools than as
medicine. That fact has not deterred the hucksters. Sales of probiotic foods
and supplements have quadrupled since 1998, and it is estimated that they will
grow even faster during the next few years. It’s nearly impossible to walk into
a grocery store without encountering some product described as a “probiotic.”
(My local store, for instance, offers such samplings as Renew Life’s Ultimate
Flora Plus Fiber, for digestive relief, which the box says contains ten billion
live cultures; Ultimate Flora Adult Formula, with fifteen billion live cultures
per capsule; and Ultimate Flora Critical Care, with fifty billion cultures in a
single pill.) “I am hopeful about the future of probiotics,’’ Blaser told me. “But
they have to be based on science. Current products are ninety-nine per cent
marketing.”
The
Culturelle ad claims that its active ingredient, Lactobacillus GG, has
been shown to “survive those good-bacteria-gobbling stomach acids and
successfully stick to the intestinal walls where it’s needed most.” Studies
have indicated that Lactobacillus GG is indeed a “good” bacterium—most
of the time. But the relationship between humans and our microbial tenants is
never simple. The American Academy of Microbiology, for example, has reported
that although Lactobacillus GG appears to reduce the risk of eczema
in babies, it can worsen the condition of people with Crohn’s disease, and in
rare cases it could cause endocarditis, a potentially deadly inflammation of
the inner layers of the heart.
Eventually,
it may become possible to restore the health of a depleted microbiome simply by
swallowing a capsule crammed with billions of bacterial cells, or by eating
yogurt. At the moment, however, not a single probiotic for sale in the United
States has been approved as a drug; instead, probiotics are sold as dietary
supplements or as foods like yogurt. This permits supplement manufacturers to
make almost any claim about the benefits of the products as long as the
packaging includes, usually in the tiniest possible type, this disclaimer: “These
statements have not been evaluated by the Food and Drug Administration. This
product is not intended to diagnose, treat, cure, or prevent any disease.”
That
kind of latitude gives customers little guidance. Joseph Mercola maintains one
of the most popular alternative-health Web sites in America, and he is
particularly bullish on probiotics. Without offering any evidence, his Web site
tells potential customers that if you buy his Complete Probiotics, and take two
capsules “15-30 minutes prior to eating breakfast,” you will give “70+ billion
colony-forming units time to prep your digestive system for what you’re about
to eat.’’ Complete Probiotics contains ten strains of bacteria, and Mercola’s
logic, shared by many other manufacturers, seems to be that if each of the
strains is beneficial on its own it will be that much more powerful when
combined with others.
“That
argument is fallacious, and potentially very troublesome,” Michael Fischbach,
of U.C.S.F., told me. He noted that although some antibiotics, taken together,
enhance each other’s effectiveness, the opposite is also true: some common
drugs are deadly when combined. “Therapeutics based on bacterial cells will
never take off until physicians feel confident that they can prescribe them as
medicine, without problems,’’ Fischbach said. “Right now, the standard for
evidence is disgustingly low. If we expect the knowledge we gain from the
microbiome to transform human health, that will have to change. If not,
probiotics will be nothing more than snake oil.”
This
week, Martin Blaser will address a plenary session of the Infectious Diseases
Society of America, an organization that he once led. The title of his talk, “The
Menace of Antibiotics,” would have generated guffaws and outrage twenty years
ago. Even today, it is easy to misconstrue his message. “We are an endlessly
variable stew of essential microbes,’’ he told me. “And they are working in
ways we have not yet understood. Antibiotics are so miraculous that we have
been lulled into a belief that there is no downside. But there is: they kill
good bacteria along with the bad bacteria.” The implication is that good
bacteria actually act as antibiotics—and are often more effective that those we
buy at a drugstore. But the microbiome is never static or simple; often it’s a
battleground between species. The difficult job of medicine is to control that
battleground
Whether
a microbe like H. pylori is dangerous or beneficial will always
depend on the ecological context in which it is found. In 1998, Blaser was
asked by the British Medical Journal to contribute to a special
series devoted to the future of medicine. He wrote that one day doctors would
begin to give Helicobacter pylori back to children—so that they would
have them, just as our ancestors did. “I am more convinced of that today than I
have ever been,’’ he said. “We will need to make sure that pregnant women have
the appropriate microbial communities to pass on to their children. If they don’t,
we will have to give them to the kids after they are born. Then, for certain
bacteria, like Helicobacter, at the age of thirty or forty, they could go
to a clinic and have them eradicated. That way, people can get the benefit of
these organisms in early life without having to pay the cost as they age.
“This has got to be an important part of the future of medicine,”
he said. “Nothing else makes sense.”
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