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发帖数: 94 | 1 原文：http://www.wired.com/2014/04/missing-microbes-antibiotic-resistance-birth/
BY MARTIN J. BLASER 04.03.14 | 6:30 AM | PERMALINK
Throughout the animal kingdom, mothers transfer microbes to their young
while giving birth. Different species of tadpoles acquire specific skin
bacteria from mother frogs even though they all live in the same pond with
the same bacterial background. Emerging chicken eggs get inoculated with
microbes from a bacteria-filled pouch near the mother hen’s rectum. And for
millennia, mammalian babies have acquired founding populations of microbes
by passing through their mothers’ vagina. This microbial handoff is also a
critical aspect of infant health in humans. Today it is in peril.
The Symbiotic Relationship Between Microbes and Mothers
Microbes play a hidden role in the course of every pregnancy. During the
first trimester, certain species of bacteria become overrepresented while
others become less common. By the third trimester, just before the baby is
born, even greater shifts occur. These changes, involving scores of species,
are not random. The compositions change in the same direction across the
dozens of women who have been studied.
Many physiological and pathological features of pregnancy are controlled, at
least in part, by the mother’s resident microbes, which evolved to help
her and themselves. When food is in short supply during pregnancy, as has
often occurred in human history, the mother’s microbes will shift their net
metabolism so that more calories flow from food to her body. In this way,
her microbes increase the odds that there will be a next generation, one
that will provide a new home for them.
Thus shifts in microbial composition may be partially responsible for those
extra pounds a mother gains, as well as for the increased sugar or glucose
levels that commonly occur during pregnancy. It makes sense; mothers store
more energy to optimize the success of their newborns.
As microbes in the mother’s intestinal tract store up energy, another
population of microbes—this time in her vagina—begins shifting as well.
Women of reproductive age carry bacteria, primarily lactobacilli, which make
the vaginal canal more acidic. This environment provides a hardy defense
against dangerous bacteria that are sensitive to acid. Lactobacilli also
have evolved a potent arsenal of molecules that inhibit or kill other
bacteria.
During pregnancy, these tiger-mother lactobacilli flourish, crowding out
other resident species and potential invaders. They are gearing up for the
main event—birth. When the mother’s water breaks, a rush of fluid is
unleashed, sweeping up bacteria as it flows onto her thighs. This splash,
now dominated by lactobacilli, rapidly colonizes the mother’s skin.
Whether the birth is fast or slow, the formerly germ-free baby soon comes
into contact with the lactobacilli. The baby’s skin is a sponge, taking up
the vaginal microbes rubbing against it. The first fluids the baby sucks in
contain mom’s microbes, including some fecal matter. Labor is not an
antiseptic process, but it has been going on like this for a long time—at
least 70 million years since our earliest mammalian ancestors.
Once born, the baby instinctively reaches his mouth, now full of
lactobacilli, toward his mother’s nipple and begins to suck. The birth
process introduces lactobacilli to the first milk that goes into the baby.
This interaction could not be more perfect.
Lactobacilli and other lactic acid–producing bacteria break down lactose,
the major sugar in milk, to make energy. The baby’s first food is a form of
milk called colostrum, which contains protective antibodies. The
choreography of actions involving vagina, baby, mouth, nipple, and milk
ensures that the founding bacteria in the baby’s intestinal tract include
species that can digest milk for the baby.
These species are also armed with their own antibiotics that inhibit
competing and possibly more dangerous bacteria from colonizing the newborn’
s gut. The lactobacilli become the earliest organisms to dominate the infant
’s formerly sterile gastrointestinal tract; they are the foundation of the
microbial populations that succeed them. The baby now has everything it
needs to begin independent life.
Breast milk, when it comes in a few days later, contains carbohydrates,
called oligosaccharides, that babies cannot digest. But specific bacteria
such as Bifidobacterium infantis, another foundational species in healthy
babies, can eat the oligosaccharides. The breast milk is constituted to give
favored bacteria a head start against competing bacteria.
The Cost of Modern Medical Miracles
Cesarian delivery is a largely unrecognized threat to the microbial handoff
from mother to child. Instead of traveling down the birth canal picking up
lactobacilli, the baby is surgically extracted from the womb through an
incision in the abdominal wall.
When the mother’s or baby’s life is in danger for any reason, emergency C-
sections are performed, often with short notice. Physicians also influence
their patients’ choices. Some are very conservative when they see any signs
of fetal stress or suspect that the mother will have problems. On a more
cynical note, it takes less time and fuss to do a C-section than to wait out
a vaginal birth. And most doctors and hospitals make more money from
performing C-sections than from natural births.
For all of these reasons, U.S. C-section rates increased from fewer than one
in five births in 1996 to one in three births in 2011—a 50 percent
increase. If this trend continues, half of all U.S. babies (2 million a year
) might be delivered surgically by 2020.
But so what? Why not perform a Cesarian if it makes the mother more
comfortable and is easier on the physician, if there is no cost other than
the hospital bill? Well, there is a cost—a biological one—and it affects
the baby.
A few years ago in Puerto Ayacucho, Venezuela, my wife, Gloria, conducted
the first study of its kind to test whether the microbes found on newborn
babies delivered vaginally or by C-section varied in any way.
Nine women participated. Four mothers delivered naturally and five had C-
sections. Gloria sampled each mom’s skin, mouth, and vaginal microbes one
hour before delivery. By DNA sequencing, she showed that the women all had
similar proportions of the major bacterial groups present at each site.
Each baby’s skin, mouth, and nose were sampled less than 15 minutes after
birth. She sampled their first stool, called meconium, 24 hours later.
The mouths, skin, and first bowel movements of babies born vaginally were
populated by their mother’s vaginal microbes: Lactobacillus, Prevotella, or
Sneathia species. Those born by C-section harbored bacterial communities
found on skin, dominated by Staphylococcus, Corynebacterium, and
Propionibacterium.
In other words, their founding microbes bore no relationship to their mother
’s vagina or any vagina. At all the sites—mouth, skin, gut—their microbes
resembled the pattern on human skin and organisms floating in the air in
the surgery room. They were not colonized by their mother’s lactobacilli.
The fancy names of these bacteria don’t matter as much as the notion that
the founding populations of microbes found on C-section infants are not
those selected by hundreds of thousands of years of human evolution or even
longer.
How Safe Is Too Safe?
Another threat to a baby’s newly acquired resident microbes involves
antibiotics given to the mother. Most doctors consider it safe to prescribe
penicillins for all sorts of mild infections in pregnancy—coughs, sore
throats, urinary tract infections. Sometimes when doctors think that the
mother has a viral infection they also give antibiotics just in case it is
actually a bacterial infection.
As we know, the antibiotics affect the mother’s resident microbes,
inhibiting susceptible bacteria and selecting for resistance. The closer the
dose is to birth, the greater the possibility that she will pass a skewed
population of microbes to her baby.
Then comes the birth itself. Women in labor routinely get antibiotics to
ward off infection after a C-section. Antibiotics are also used to prevent a
serious infection in newborns caused by Group B strep, a bacterium that
between a quarter and a third of U.S. pregnant women carry. It lives in the
gut, mouth, skin, and sometimes the vagina and rarely causes any problem in
the mother. But sometimes Group B strep can be lethal to newborns’ fragile
immune systems. While such infections are uncommon, professional groups
recommend that all pregnant women be screened for the microbe near the time
of delivery. If they are positive, they get a dose of an antibiotic shortly
before the baby descends the birth canal.
Each year in the United States well over a million pregnant women are Group
B strep–positive, and all will get intravenous penicillin during labor to
protect their babies. But only one in 200 babies actually gets ill from the
Group B strep acquired from his or her mother. To protect one child, we are
exposing 199 others to antibiotics.
The problem, of course, is that we know antibiotics are broad in their
effects, not targeted. While the antibiotic kills Group B strep, it also
kills other often-friendly bacteria, thus selecting for resistant ones. This
practice is altering the composition of the mother’s microbes in all
compartments of her body just before the intergenerational transfer is
slated to begin.
The baby also is affected in similar unintended ways. Any antibiotic that
gets into the bloodstream of the fetus or into the mother’s milk will
inevitably influence the composition of the baby’s resident microbes, but
we are only beginning to understand what this means.
Finally, the babies are directly exposed. Most parents are not aware that
all American-born babies today are given an antibiotic immediately after
birth. The reason is that many years ago, before antibiotics, women who
unknowingly had gonorrhea would pass the infection to their babies, giving
the newborns terrible eye infections that could cause blindness.
So 4 million babies born in the United States every year are given
antibiotic eye-drops to prevent an illness that occurs very rarely. The dose
is low but is likely affecting the composition of the infant’s resident
microbes just when the founding populations are developing. We should be
able to develop a better way to screen, so we can target those babies at the
highest risk, perhaps a few hundred among the millions of births a year.
Although babies are born into a world replete with diverse bacteria, the
ones that colonize them are not accidental. These first microbes colonizing
the newborn begin a dynamic process. We are born with innate immunity, a
collection of proteins, cells, detergents, and junctions that guard our
surfaces based on recognition of structures that are widely shared among
classes of microbes. In contrast, we must develop adaptive immunity that
will clearly distinguish self from non-self. Our early-life microbes are the
first teachers in this process, instructing the developing immune system
about what is dangerous and what is not.
In our first three years of life, a great diversity of microbes self-
organizes into a life-support system with the complexity of the adult
microbiota. This critical period lays the foundation for all the biological
processes that unfold in our childhood, adolescence, adulthood, and old age
—unless something comes along to disrupt it.
Adapted and excerpted from Missing Microbes: How the Overuse of Antibiotics
Is Fueling Our Modern Plagues. Copyright 2014 Martin J. Blaser, M.D.
Reprinted with permission from Henry Holt and Company. |
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