[The original publication in Scientific American contains
numerous links to related material. See especially the 
essay by David Relman (Stanford School of Medicine) 
in Nature:
http://www.nature.com/nature/journal/v486/n7402/full/486194a.html]
-- moderator]

Body Count: Taking Stock of All the Bugs That Call
Humans Home

     Characterizing the diverse human microbiome may
     someday help us avoid disease and boost health

By Katherine Harmon
June 13, 2012
http://www.scientificamerican.com/article.cfm?id=microbiome-survey

The microbes that inhabit our bodies are intimately
involved in human health and disease yet we still know
relatively little about them. A new major census of
these tiny symbionts has revealed that they are an even
more diverse bunch than was once presumed.

We have long focused on single bacteria as sources of
disease (E. coli or streptococcus, for example). But we
have now been learning that, for the most part, these
trillions of microbes that make their homes in and on us
do an excellent job keeping us healthy (crowding out
harmful microbes) and sated (breaking down a lot of the
food we ingest).

Now that disturbances in this rich microbiome community
have been linked to weight gain, inflammatory bowel
disease, vaginal infections and risk for infection with
harmful microbes (such as methicillin-resistant
Staphylococcus aureus, or MRSA), the importance of
understanding what makes up a "healthy" microbiome has
become even more apparent.

We have been adding names to the attendee list for
years, but scientists still do not have a full rundown
of all of the bacteria, where they live in our bodies
and their role in health and disease. "We need a
reference to say what is normal before we can say what
is abnormal," Eric Green, director of the National Human
Genome Research Institute, said in a press briefing
Wednesday.

Green and his colleagues at the Human Microbiome Project
have taken a big step forward in charting this complex
territory, publishing an extensive new survey of the
microbial profiles of hundreds of individuals. The
findings are described in two papers and an essay online
June 13 in Nature and in more than a dozen papers in
PLoS ONE. (Scientific American is part of Nature
Publishing Group.) The findings only reinforce the
suspicion that this invisible landscape is even more
nuanced-and important-than we thought. For example, each
person might carry around hundreds of thousands of
species. These bugs bring with them some eight million
different genes, which far outshines our own paltry
22,000.

"This is really a new vista on biology," Phillip Tarr,
director of pediatric gastroenterology and nutrition at
Washington University School of Medicine in Saint Louis
and a collaborator on the research, said in the press
briefing. "It opens up many opportunities to improve the
health of our population."

To get their results, the team collected samples from
242 healthy adults aged 18 to 40 living in Houston or
Saint Louis. From each person, researchers sampled 15 to
18 specific "habitats" (nine from the mouth, four from
the skin, one from the nose and three from the female
genitals) as well as from stool samples.

"Healthy humans carry a remarkable diversity of
organisms," says Bruce Birren, director of the Genomic
Sequencing Center for Infectious Diseases at the Broad
Institute and study collaborator, said at the briefing.
The oral and fecal samples had the highest microbe
diversity, whereas the vaginal samples had the lowest.

Each person had a relatively different microbiome,
reinforcing the notion that there is no single "healthy"
microbiome profile. "Apparently there are many different
ways to be healthy when it comes to our microbes,"
Birren said. The group found that even with so many
different microbial communities at each location, the
same metabolic functions seem to be getting done. Birren
likens it to a potluck dinner, where everyone brings
something different to the table so everyone gets to
eat.

More than half of the study subjects had samples
collected a month to a year following the initial
collection and some had three samples taken. In general,
microbial populations present in the first sample were
there in the last one as well and did not show any big
blooms in the study subjects.

Getting a sense of which microbes are living in our
intestines turns out to be a much more complicated task
than simply looking at slides under a microscope. Many
of the microbes that live inside our bodies don't do
well in an oxygen-filled lab environment, so they have
proved difficult to culture. This project sidestepped
that problem by using genetic sequencing to catalogue
species by their genetic profiles instead.

The question, however, of how to measure, track and
count these organisms that we know so little about also
presents some research dilemmas. One method researchers
used to identify different species involves tracking the
bacterial 16s gene, which humans lack. This gene appears
to be different enough in each bacterial species to
allow for rapid scanning and sorting of the organisms.
The effectiveness of this detection method remains
unclear. "In some ways, we're simply counting different
features that are easiest for us to measure, but we
don't know that those are the most important things,"
says David Relman, of the Stanford School of Medicine,
who was not involved in the new studies but wrote an
essay about them in the same issue of Nature.

Nevertheless, Relman notes, the findings are important
early first steps, which will help inform and streamline
later research. "I think it would be hubris to say this
project answers something or provides the end of the
story," he says. Coming work will need to zero in on
individual variables, such as diet, environment and
health status, to look more closely for trends in
microbiome communities.

Tarr suggested that better understanding what a healthy
microbiome looks like, for example, could help us
prevent virulent infections, such as Clostridium
difficile. C. diff is often acquired in a hospital. Our
best preventative weapon so far has been better hygiene,
and our treatments are only mediocre. But, he noted, if
we could find out the characteristics of a microbiome
that puts people more at risk for acquiring a difficult
C. diff infection, we could theoretically screen
incoming patients for their microbiome's genetic profile
at admission, heading off potentially fatal infections.

These "who's who" lists of our microbiome "are
potentially useful and biologically important as a frame
of reference, but they do not tell you what the microbes
are actually doing at any one time," notes Jeremy
Nicholson, head of the Department of Surgery and Cancer
at Imperial College London, who was not involved in the
most recent studies. He and his colleagues published a
study in Science last week examining some of the
metabolic interactions of the microbes in the human gut
and their host. "To understand them functionally as part
of the big human health picture," he notes, we will need
a more detailed picture of how human diet and
lifestyles-including stress and medications-are
impacting the microbial communities, along with how
their changes are then changing us. "Understanding these
interactions is where the new therapies are to be
found."

Another study, published online today in Nature, reveals
how a diet high in saturated fat can, in fact, change
the microbial communities in the gut. This shifting
population can spur an immune response that can lead to
inflammatory bowel disease in those who are genetically
prone.

A better picture of these kinds of interactions should
help us better understand how microbes help us
metabolize food as well as drugs, Nicholson notes. "So
the sky is the limit in terms of potential therapeutic
interventions if we can understand all this complexity,"
he says. "This is going to be a major part of
personalized health care in the future."

For another Human Microbiome Project collaborator,
Baylor College of Medicine's Amy McGuire, the findings
of the vast accumulation of varied microbes that live in
all of us presents an additional existential facet: "It
changes how we think about what it means to be human."

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