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Human Microbiome May Be Seeded Before Birth

We are each home to about 100 trillion bacteria, which we carry with us from birth till death. But when
Juliette C. Madan was trained as a neonatologist in the mid-2000s, her teachers told her in no
uncertain terms that we only acquire those bacteria after we are born. It was clear as day, we were
told, that fetuses were sterile, she said.
Dr. Madan is now an assistant professor of pediatrics at the Geisel School of Medicine at Dartmouth,
and shes come to a decidedly different view on the matter. I think that the tenet that healthy fetuses
are sterile is insane, she said.
Dr. Madan and a number of other researchers are now convinced mothers seed their fetuses with
microbes during pregnancy. They argue that this early inoculation may be important to the long-term
health of babies. And manipulating these fetal microbes could open up new ways to treat medical
conditions ranging from pre-term labor to allergies.
In 1900, the French pediatrician Henry Tissier declared unborn babies bacteria-free. Only when they
started their journey down through the birth canal did they begin to get covered with microbes. The
newborns then acquired more as they were handled and nursed.
Photo

Credit David Fairfield/Getty Images

This was considered a kind of scientific dogma, said Esther Jimnez Quintana of Complutense
University of Madrid.
This dogma gained strength from studies on babies born prematurely. Infections are a major risk
factor in early labor. Many researchers saw this as evidence that the only bacteria in the uterus were
dangerous ones.
But scientists came to this conclusion without finding out whether healthy fetuses had bacteria, too. It
became a self-fulfilling prophecy, said Dr. Madan.
That has started to change in the past few years. In 2010, Josef Neu, a University of Florida
pediatrician, examined the first stool from newborn babies, before they had their first meal. He found a
diversity of bacteria in the stool, whether the babies were born on time or born prematurely.
When we first saw this, we though it was an artifact, said Dr. Neu. If the fetuses were indeed sterile,
their stool should have been germ-free. But in follow-up studies, he has gotten the same results.

Other scientists have also found evidence indicating that healthy fetuses pick up bacteria in the womb.
Dr. Quintana and her colleagues have found bacteria in the amniotic fluid of healthy babies, as well as
in umbilical cord blood and placentas.
If other animals are any guide, we shouldnt be surprised if human fetuses are laced with bacteria. In
an essay published last week in the journal PLOS Biology, Seth R. Bordenstein and Lisa J. Funkhouser
of Vanderbilt University observed that mothers transmitting bacteria to their offspring is the rule
rather than the exception in the animal kingdom. Studying other species may give scientists clues
about how human mothers inoculate their unborn children.
Photo

Carl Zimmer Credit Earl Wilson/The New York Times

One open question is the route that bacteria take from mothers to their fetuses. A number of
researchers suspect that immune cells in the mothers intestines swallow up bacteria there and ferry
them into the bloodstream, where they eventually wind up in the uterus.
Its also not clear whether mothers deliver a random collection of species or a special set that are

beneficial to them. Studies on children and adults have shown that our resident bacteria collectively
known as the microbiome help us in many ways. They digest compounds in our food that would
otherwise be indigestible.
Beneficial bacteria also help tutor the immune system, so that it attacks pathogens without
overreacting and damaging the body itself. The microbiome can even fend off disease-causing bacteria.
Dr. Neu and other pediatricians are now investigating whether the microbiome helps fetuses before
birth. He speculates that a healthy supply of bacteria in a fetus can reduce the chances of premature
birth. If harmful bacteria manage to slip past those defenses, they may trigger an immune reaction that
is sensed by the mother, prompting her to go into labor.
As scientists investigate the microbiome, they are also exploring ways of manipulating it to treat
disorders ranging from gut infections to autoimmune disorders. Dr. Neu hopes it may be possible
someday to bring the same medical help to fetuses.
We might provide mothers with a microbial cocktail, he said. The bacteria would pass from a mother
to her fetus. Doctors might prescribe certain species to protect the fetus from infections, warding off
early labor. Nurturing the fetal microbiome could help babies in other ways, like boosting their
immune system.
Some scientists dont think the evidence supports these ideas, though. Bacteria in fetuses may not have
any special role to play in their health. It could just be part of the vulnerabilities that pregnancy poses
on the maternal body, said Maria Dominguez-Bello, an associate professor at N.Y.U. Langone Medical
Center.
But figuring out which explanation is right will demand the careful study of healthy fetuses
something that has only barely begun.
The frontier is ahead of us, said Dr. Bordenstein.
Matter
Matter. Its the stu of
everything large and
small.

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