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Microbial Menagerie

A massive study catalogues the microbes in the healthy human body, uncovering an unexpected level of individual variation in microbial makeup, among other surprises.

By | June 13, 2012

Escherichia coliROCKY MOUNTAIN LABORATORIES, NIAID, NIH

The human body is largely not human. It contains trillions of microbes that outnumber out own cells 10 to 1, affecting our health and behavior. Now, an international consortium of around 200 scientists has mapped this diverse microbial community at an unprecedented level of detail, and shown just how much it varies from person to person.

“This represents a yet another milestone that will help to expand our knowledge about the invisible world of human-associated microbes,” said Peer Bork from the European Molecular Biology Laboratory, who was not involved in the study.

The team, working together as part of the Human Microbiome Project (HMP), studied the microbes of 242 healthy volunteers, aged 18 to 40. They collected samples from 18 body parts for women and 15 for men, from the nostril to the crease behind the ear—habitats as different to bacteria as deserts or jungles are to us.

“The project has surveyed more body sites, in more individuals, with greater depth of sequencing than any previous study,” said Curtis Huttenhower from the Harvard School of Public Health, who is the lead author on one of two papers that describe the main results, published today in Nature. Many other papers, published in PLoS journals, describe the denizens of specific body parts.

In cataloguing the healthy human microbiome, the HMP has already yielded some surprises. For example, although each body part is characterised by some signature microbial groups, no species was universally present across every volunteer. “One of the HMP's original mandates was to define the core microbiome, or the bugs that everyone shares,” said Huttenhower. “It looks like there really aren't any.”

And microbe species that were shared across people still differed in terms of specific strains and genetic make-up of those strains. “Even when we carry the ‘same’ microbes, they seem to have small differences between their genomes just like people do,” Huttenhower said.

However, these varied microbes carry out overlapping jobs, including creating and breaking down nutrients. “This incredible species diversity leads to an incredible conservation at the level of molecular function,” said Rob Knight from the University of Colorado in Boulder, who was part of the consortium. “This suggests different bugs are performing the same jobs in different people, just like every city has bankers and lawyers and salesmen that make the city's ecology tick,” said Huttenhower.

While major disease-causing microbes were very rare, all the volunteers, even though they passed a rigorous health screen, carried opportunistic pathogens—microbes like Staphylococcus aureus that are normally harmless but occasionally go rogue and cause disease. This parallels the situation in our own genome, where genetic variants that confer a high risk of disease are rare, while those that pose a moderate risk are more common.

The HMP team revealed that our microbial communities are most diverse in the mouth and the gut, and least so in the vagina. They also showed that these communities are very stable over time, by sequencing extra samples from 131 of their volunteers after several months.

“We are similar yet different, but stable in our differences,” said Dusko Ehrlich from Institut National de la Recherche Agronomique (INRA), who was not involved in the study. “If we were all the same, there’d be no signal. If we were all different, you couldn’t do a comparison. If we changed all the time, there would be too much of a moving target. Instead, we have hope for capturing interesting differences that matter for our health.”

So far, the HMP has accumulated around 3.5 terabytes of data, all accessible through public databases. “It’s a real treasure trove,” said Ehrlich.

Still, “there is a lot of work ahead to understand the data,” Bork noted. For example, what causes the individual differences in microbial diversity? Age, gender, and body weight only explain a fraction of the total variation, and other factors such as diet, geography and host genetics probably play a role too.

Despite the variation, the HMP still aims to characterize a “healthy” Western microbiome, which could be used to understand how and why the microbiome changes with disease, and how it interacts with our own cells and genes. Such studies are close to providing new diagnostic tools, and may lead to new ways of treating diseases, said Huttenhower. “The human genome's taken a decade to be translated into clinical practice, and the same process is already beginning for the microbiome,” he said. “It will be very exciting to see the field of microbiome research also start to influence personalized medicine.”

The Human Microbiome Project Consortium, “Structure, function and diversity of the healthy human microbiome,” Nature, 486: 207-214, 2012.

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Avatar of: Hilary Butler

Hilary Butler

Posts: 1457

June 14, 2012

And given that it has been shown that antibiotics destroy the unique microbiome, sometimes permanently, that raises some questions:

1) Were the authors studying people who regularly took antibiotics, and comparing them with those who don't?

2) If so, were there any major differences within the two groups?

3) Given that bacteria play a huge role in our inate immune system orchestration, and some studies have shown that every course of antibiotics increases the risk of cancer, exactly WHAT is the protective role of the microbiome in human health as a whole?

Avatar of: Guest

Anonymous

June 14, 2012

Questions of whether man-made antibiotics or natural antibiotics permanently alter the varieties or ratios of varieties of flora and fauna at certain portions of the human alimentary canal... are not issues on those merits, alone.

The more significant issues surround what we could called "therefore what?" questions.

Such questions do not reduce to, "What does bacterium A do when it is the only bacterium in the human alimentary canal?" The REASON such reduction cannot be made, experimentally, is because no one bacterium ever occurs to itself alone, in and throughout an alimentary canal.

Flora and fauna occupy the human gut in complex combinations.  And, I respectfully submit, the only meaningful way to study varieties of admixtures, at various ratios, is through data-driven study.  What is more, the numbers, ratios of numbers and particular kinds of flora and fauna that occupy one section of the gut of one individual tend to differ not only from one organism within a species and another but ALSO from one area of the gut to another in a single host, and even this changes over time... whatever may be the etiology of such temporal variation.

How, then, can the benefit or detriment of so many kinds of micro-biotic species be evaluated for medical-purposes? 

There is only one way, by collecting gazillions of samples of populations from many individuals, from the same individuals over time, and following the medical history of subjects from whom samples have been drawn for the rest of the subjects lives, and THEN allowing DATA-DRIVEN patterns to be searched for -- as well as hypothesis-driven ones.  In fact, I would suggest that allowing a pattern-recognition type program to do some "open-ended" searching will SAVE TIME.  Why?  Because we could spend a thousand years trying to prove everything we might brainstorm up, before we would discover something right under our noses that we had not intuited to be a likelihood.

What is more, we would need to feed into our open-ended pattern search not only such data as would seek correlations between good vs. bad or better versus worse medical histories at relating to what combinations of bacteria are where, and in whom, and when in relation to what pathologies do or do not follow but, also, such additional factors as whether, say, a patient has been a smoker, whether he or she consumes excessive amounts of alcohol, what differences and similarities in diet and comparative calorie consumption particular individuals practice, whether each subject is male or female, what her weight is at various points along the way, whether he or she has dental caries or gum inflammation or IBS or any other chronic gut condition is present, or allergies or variations of pH between individuals, or in the same individual over time...or... hey... you name it.

Is such research possible?  Well, technically, yes!  But it would/will take many, many years of data gathering before a sufficiently representative sampling could be fed into a data processing system with a pattern-finding program capable of discovering correlations of interest.  And then some interpretation would be required to establish situations in which correlations are, or are not, indicators of cause and effect.

In the meantime, about the best we can do is look for large, simple, obvious correlations, and consider some treatment options based on what might be likely to make a medically desirable difference.  

What is of little, if any, value or use, is speculation about whether the taking of certain medications, by altering gut flora and fauna variables, is good, bad or indifferent.  And, after all, there are numerous instances in which treatment protocols introduce a trade-off -- where, for example, known side-effects of taking a pharmaceutical that will save the patient from one undesirable syndrome may predispose the patient to risk from some other danger -- for example, when a tumor is treated with radiation, and the radiation raises the risk of causing other oncological mutations among other cells, or when the immune system is shut down to prevent it from cancelling out one kind of treatment, and raises the risk of the patient's being harmed by some other infection (even some normally-benign bacterium in the gut that the immune system may have kept quiescent).

Simplistic scare talk about what antibiotics do, or don't do, in the context of so many variable as confront researchers and medical professionals -- and so many complexities as we are as yet unable to parse -- is about as useful as trying to deal with hurricanes by blowing hot air against the wind.

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