100 Trillion Bacteria: Humans are More Environments than Organisms

note: this is a point I often raise in my sun-moon-earth alchemy/Greater Kan Li course: the planetary mass is five-sixths dead bacteria, and human’s are ecosystems that mimic that…..

THE BODY POLITIC

By Courtney Humphries
Seed Magazine
April 14, 2009

http://seedmagazine.com/content/print/the_body_politic/

The deep symbiosis between bacteria and their human hosts is forcing
scientists to ask: Are we organisms or living ecosystems?

…………..

As soon as we are born, bacteria move in. They stake claims in our digestive
and respiratory tracts, our teeth, our skin. They establish increasingly
complex communities, like a forest that gradually takes over a clearing. By
the time were a few years old, these communities have matured, and we carry
them with us, more or less, for our entire lives. Our bodies harbor 100
trillion bacterial cells, outnumbering our human cells 10 to one. Its easy
to ignore this astonishing fact. Bacteria are tiny in comparison to human
cells; they contribute just a few pounds to our weight and remain invisible
to us.

Its also been easy for science to overlook their role in our bodies and our
health. Researchers have largely concerned themselves with bacterias
negative role as pathogens: The devastating effects of a handful of
infectious organisms have always seemed more urgent than what has been
considered a benign and relatively unimportant relationship with good
bacteria. In the intestine, the bacterial hub of the body that teems with
trillions of microbes, they have traditionally been called commensal
organisms–literally, eating at the same table. The moniker suggests that
while weve known for decades that gut bacteria help digestion and prevent
infections, they are little more than ever-present dinner guests.

But theres a growing consensus among scientists that the relationship
between us and our microbes is much more of a two-way street. With new
technologies that allow scientists to better identify and study the
organisms that live in and on us, weve become aware that bacteria, though
tiny, are powerful chemical factories that fundamentally affect how the
human body functions. They are not simply random squatters, but organized
communities that evolve with us and are passed down from generation to
generation. Through research that has blurred the boundary between medical
and environmental microbiology, were beginning to understand that because
the human body constitutes their environment, these microbial communities
have been forced to adapt to changes in our diets, health, and lifestyle
choices. Yet they, in turn, are also part of our environments, and our
bodies have adapted to them. Our dinner guests, it seems, have shaped the
very path of human evolution.

In October, researchers in several countries launched the International
Human Microbiome Consortium, an effort to characterize the role of microbes
in the human body. Just over a year ago, the National Institutes of Health
also launched its own Human Microbiome Project. These new efforts represent
a formal recognition of bacterias far-reaching influence, including their
contributions to human health and certain illnesses. This could be the basis
of a whole new way of looking at disease, said microbiologist Margaret
McFall-Ngai at the 108th General Meeting of the American Society for
Microbiology in Boston last June. But the emerging science of human-microbe
symbiosis has an even greater implication. Human beings are not really
individuals; theyre communities of organisms, says McFall-Ngai. Its not just
that our bodies serve as a habitat for other organisms; its also that we
function with them as a collective. As the profound interrelationship
between humans and microbes becomes more apparent, the distinction between
host and hosted has become both less clear and less important–together we
operate as a constantly evolving man-microbe kibbutz. Which raises a
startling implication: If being Homo sapiens through and through implied a
certain authority over our corporeal selves, we are now forced to relinquish
some of that control to our inner-dwelling microbes. Ironically, the human
ingenuity that drives us to understand more about ourselves is revealing
that were much less human than we once thought.

To find a biological answer to the question Who are we? we might look to the
human genome. Certainly, when the Human Genome Project first produced a
draft of the 3 billion-base-pair sequence, it was touted as a blueprint for
human life. Less than a decade later, however, most experts recognize that
our genomes capture only a part of who we are. Researchers have become
aware, for example, of the influence of epigenetic phenomena–imprinting,
maternal effects, and gene silencing, among others–in determining how
genetic material is ultimately expressed. Now comes the notion that the
genomes of microbes within us must also be considered. Our bodies are, after
all, composites of human and bacterial cells, with microbes together
contributing at least 1,000 times more genes to the whole. As we discover
more and more roles that microbes play, it has become impossible to ignore
the contribution of bacteria to the pool of genes we define as ourselves.
Indeed, several scientists have begun to refer to the human body as a
superorganism whose complexity extends far beyond what is encoded in a
single genome.

The physiology of a superorganism would likely look very different from
traditional human physiology. There has been a great deal of research into
the dynamics of communities among plants, insect colonies, and even in human
society. What new insights could we gain by applying some of that knowledge
to the workings of communities in our own bodies? Certain body functions
could be the result of negotiations between several partners, and diseases
the result of small changes in group dynamics–or of a breakdown in
communication between symbiotic partners.

Recently, for instance, evidence has surfaced that obesity may well include
a microbial component. In ongoing work that is part of the Human Microbiome
Project, researchers in Jeffrey Gordons lab at the Washington University
School of Medicine in St. Louis showed that lean and obese mice have
different proportions of microbes in their digestive systems. Bacteria in
the plumper rodents, it seemed, were better able to extract energy from
food, because when these bacteria were transferred into lean mice, the mice
gained weight. The same is apparently true for humans: In December Gordons
team published findings that lean and obese twins–whether identical or
fraternal–harbor strikingly different bacterial communities. And these
bacteria, they discovered, are not just helping to process food directly;
they actually influence whether that energy is ultimately stored as fat in
the body.

Even confined in their designated body parts, microbes exert their effects
by churning out chemical signals for our cells to receive. Jeremy Nicholson,
a chemist at Imperial College of London, has become a champion of the idea
that the extent of this microbial signaling goes vastly underappreciated.
Nicholson had been looking at the metabolites in human blood and urine with
the hope of developing personalized drugs when he found that our bodily
fluids are filled with metabolites produced by our intestinal bacteria. He
now believes that the influence of gut microbes ranges from the ways in
which we metabolize drugs and food to the subtle workings of our brain
chemistry.

Scientists originally expected that the communication between animals and
their symbiotic bacteria would form its own molecular language. But
McFall-Ngai, an expert on animal-microbe symbiosis, says that she and other
scientists have instead found beneficial relationships involving some of the
same chemical messages that had been discovered previously in pathogens.
Many bacterial products that had been termed virulence factors or toxins
turn out to not be inherently offensive signals; they are just part of the
conversation between microbe and host. The difference between our
interaction with harmful and helpful bacteria, she says, is not so much like
separate languages as it is a change in tone: Its the difference between an
argument and a civil conversation. We are in constant communication with our
microbes, and the messages are broadcast throughout the human body.

The first study of a microbial community living on the human body was made
back in 1683, when Antony van Leeuwenhoek wrote a letter to the Royal
Society including his observations through the microscope of his own dental
plaque, in which he described seeing many very little living animalcules,
very prettily a-moving. But despite this very early interest in the microbe
communities on the body, over the next three centuries, microbiologists
focused mainly on isolating bacteria: removing them from their natural
contexts and growing them in culture dishes in the lab. This approach was
the only way to observe and understand bacterial cells in great detail. But
it also created huge gaps in knowledge about bacterial life. It focused on
the fraction of microorganisms that can be grown in culture, and it
overlooked the highly complex and diverse ways in which they actually live
together–an approach akin to studying humans by confining them in prison
cells while ignoring the cities and communities that make up their natural
habitat.

This narrow view of microorganisms began to change when new genetic
sequencing technologies–which fished the genes directly out of water or
soil samples–made it possible to collect information about microorganisms
without having to isolate them. These studies revealed an incredible amount
of genetic abundance and diversity; the microbial world was a far bigger and
denser landscape than anyone had previously known. A further leap in
technology has been the ability to sequence large numbers of genes rapidly.
Even without seeing the organisms themselves, scientists can now sequence
tens or hundreds of thousands of genetic fragments from an environmental
sample. The resulting science of metagenomics eschews traditional ideas
about studying the natural history of a particular organism in favor of a
global view of the genes that exist in a community.

Using these new metagenomic methods, environmental microbiologists have
delved into uncharted territories–acidic lakes, deep-ocean hydrothermal
vents, and frozen tundra, to name but a few–to see what life might exist
there. Gradually, some have applied the new tools to explore the
environments of humans and other animals, with recent surveys, for instance,
of the bacterial communities in various microclimates of the human body,
from rear molars to intestines to nasal passages. And with these studies and
the launch of the Human Microbiome Project, the fields of medical and
environmental microbiology have begun to merge. The resulting hybrid
discipline embraces the complexity of a larger system; its integrative
rather than reductive, and it supports the gathering view that our bodies,
and the bodies of other animals, are ecosystems, and that health and disease
may depend on complex changes in the ecology of host and microbes.

In 2007, Cornell University microbiologist Ruth Ley coauthored a paper
arguing that human microbiome studies could bridge the divide between
biomedical and environmental microbiology. Like Jeffrey Gordon, her coauthor
and mentor, Ley studies bacteria in the human gut. But while Gordon, Ley,
and their fellow microbial sleuths might have hoped for a core set of
organisms that would define the human microbiome, so far the reality is
proving far more complicated. While only a few major groups of the worlds
bacteria live in the human body, within these groups are countless bacterial
species that vary greatly from person to person. The more people look at it,
it seems like an endlessly diverse system, says Ley. The landscape of the
body presents a wide range of habitats. In the nutrient-rich land of the
intestines, communities appear to be fairly stable over time, while early
indications show the harsher environment of the skin attracting itinerant
communities that come and go. Communities can be as localized as the
neighborhoods of a city; the inner elbow contains a different group of
residents than the forearm.

Furthermore, in contrast to habitats such as the deep sea, where emigration
and immigration are rare events, many microbial communities associated with
humans are affected by constant interactions with microorganisms coming in
from the environment. Microbes in the gut, for instance, encounter bacteria
that ride in on the food we consume. These visitors introduce a huge,
unpredictable component that makes any determination of a core microbiome
all the more difficult. In order to develop well-framed research questions,
its crucial that microbiologist learn how to differentiate between
co-evolved species and these itinerant tourists.

What we do know, however, is that our own personal microbiomes tend to be
partly inherited–most of us pick up bacteria from our mothers and other
family members early in life–and partly shaped by lifestyle. Ley, who has
surveyed the gut bacteria of several species, says that diet is an important
factor in determining the communities that live in an organism. Even with
our processed foods and sterilized kitchens, Ley says, humans are not
radically different from other animals that share our eating habits.

The individuality of each persons microbiome might complicate the project of
studying human-microbe relationships, but it also presents
opportunities–for instance, the possibility that medical treatments could
be tailored to a persons particular microbiota. Much like a genetic profile,
a persons microbiome can be seen as a sort of natural identification tag. As
David Relman, a microbiologist at Stanford University, puts it, Its a
biometric–a signature of who you are and your life experience. With support
from the Human Microbiome Project, Relman is currently developing novel
microfluidic devices that can isolate and sequence the genomes of individual
bacterial cells. (Extracting genetic information from a complex sample
normally mixes together hundreds if not thousands of unique species, so this
single-microbe technology could well revolutionize the speed and scope of
the entire field of metagenomics.) Personal microbiome information will also
have implications for practical concerns, such as how we deploy antibiotics.
Might those antibiotics we down at the first sign of an upset stomach be
waging an unjustified civil war? Where do the massive quantities of
antibiotics we feed to our livestock ultimately end up, and do they disrupt
delicate ecological balances? We have lived with microbes for our entire
evolutionary history; how has the widespread use of chemicals that kill them
changed those long-forged evolutionary relationships?

Few people are more familiar with lifes interdependence and the blurriness
of its distinctions than microbiologists. The recent metagenomic studies
have revealed a daunting amount of diversity in microbial life, with none of
the clear divisions were used to in the macro world. Among bacteria, the
entire concept of species breaks down; its difficult for scientists to even
categorize what they are seeing. Microbes offer a picture of life that is
fluid and ever changing.

To come to terms with this diversity, microbiologists are today
relinquishing the desire to name names. When studying a community, they no
longer focus on developing a roster of who is there; instead, they ask what
kinds of genes are present and what their functions are. In the human
microbiome, which species we harbor may be less important than what they are
doing.

William Karasov, a physiologist and ecologist at University of
Wisconsin-Madison, believes that the consequences of this new approach will
be profound. Weve all been trained to think of ourselves as human, he says.
Bacteria have been considered only as the source of infections, or as
something benign living in the body. But now, he says, it appears that we
are so interconnected with our microbes that anything studied before could
have a microbial component that we hadnt thought about. It will take a major
cultural shift, says Karasov, for nonmicrobiologists who study the human
body to begin to take microorganisms seriously as a part of the system.

Equally challenging, though in a different respect, will be changing
long-held ideas about ourselves as independent individuals. How do we make
sense of this suddenly crowded self? David Relman suggests that how well you
come to terms with symbiosis depends on how comfortable you are with not
being alone. A body that is a habitat and a continuously evolving system is
not something most of us consider; the sense of a singular, continuous self
is a prerequisite for sanity, at least in Western psychology. A symbiotic
perspective depends on a willingness to see yourself as the product of
evolutionary timescales. After all, our cells carry an ancient stamp of
symbiosis in the form of mitochondria. These energy-producing organelles are
the vestiges of symbiotic bacteria that migrated into cells long ago. Even
those parts of us we consider human are part bacterial. In some ways, were
an amalgam and a continuously evolving collective, Relman says.

He also believes that we might have something to gain by embracing our
bacterial side. Bacteria are often dismissed as simpler, less sophisticated,
and less worthy of our consideration. We put a lot of weight on a life forms
ability to think independently, Relman says, but microbes have achieved
fantastic evolutionary success by operating on a very different principle.
Microbial communities are filled with examples of self-sacrifice for the
benefit of the larger colony. They form physically close communities in
which some cells exist solely to provide structural support or protection
for others. This intertwining of fate, as Relman puts it, is something that
humans could consider more seriously in the dynamics of their own societies,
instead of focusing so keenly on individual identity and success.

Perhaps we could learn a lesson in fluidity from our symbionts. Science is
always challenging us to let go of treasured categories and divisions. The
theory of evolution, for instance, forced us to see species as points along
a shared history, rather than as fixed identities. Symbiosis goes a step
further by showing us how species are linked by more than history; they are
living together in a continuous, interconnected now.

When scientists in 1977 first discovered life in the deep-sea hydrothermal
vents, including gigantic tubeworms living in scalding-hot water filled with
hydrogen sulfide, they could not explain it. Until then, all life was
thought to derive its energy from the sun, but this habitat was far from any
light. Then scientists found that the worms harbored symbiotic bacteria,
which fed on hydrogen sulfide, turning this poison into something usable by
other life forms. The discovery underscored the fact that life as we know it
is built upon microbes, whether we look in the deepest oceans or our own
intestines. We once had the luxury of ignoring the diminutive members of our
bodies and other ecosystems. Now the blinders are off.