TERRY GROSS, host:
I think the research I did for my next interview has permanently changed the way I see my body. I didnt realize that the overwhelming majority of cells on or in my body aren't human cells. They're microorganisms, mostly bacteria. And as creepy as that sounds, although some of those bacteria can cause disease, others might help cure or prevent disease. The vast majority of these microbes live in the intestines.
My guest, Dr. Jeffrey Gordon, is studying the microbial ecosystem of the human gut and how microbes affect digestive health, predisposition to disease and possibly obesity.
Dr. Gordon directs the Center for Genome Sciences at Washington University in St. Louis, which is in the process of sequencing the genomes of the human gut. It's a microbial version of the Human Genome Project which identified all the genes in human DNA.
Dr. Jeffrey Gordon, welcome to FRESH AIR. Give us a sense of the magnitude of microorganisms that live on or in our bodies.
Dr. JEFFREY GORDON (Director, Center for Genome Sciences, Washington University): It's rather staggering. We think that there are 10 times more microbial cells on and in our bodies than there are human cells. That means that we're 90 percent microbial and 10 percent human. There's also an estimated 100 times more microbial genes than the genes in our human genome. So we're really a compendium, an amalgamation of parts that are both human and microbial.
GROSS: There's something very upsetting about that.
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GROSS: You know, to think that only 10 percent of the cells we're carrying are only human cells and the rest are microorganisms.
Dr. GORDON: It's humbling.
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Dr. GORDON: But, of course, it's very - we have this anthropocentric view of ourselves as somehow superior as a life form. Yet, the most ancient of life is suffused on and in us. But I also think its quite natural, because all life that's appeared, all the animal life that's appeared on our planet has to adapt, has to collude and collaborate with microbes, which are the dominant life form on Earth.
GROSS: So which parts of our bodies make the best homes?
Dr. GORDON: Well, the savored place, at least in terms of number, is the human gut.
GROSS: And that's your part. That's what youre studying.
Dr. GORDON: That's right. I and know the number one trillion has lost its impact factor over the last couple of years.
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Dr. GORDON: But there are tens and tens of trillions of microbes that live in our human gut. And they're not just bacteria, but bacteria dominate.
GROSS: So you say most of the microorganisms we are carrying around are in our gut but what other parts of the body are they populating?
Dr. GORDON: All exposed surfaces, our skin, our mouth, and one of the challenges is, and we can talk about this in a minute, is to be able to determine what life exists within us and on us, how does this vary, when do we acquire it, and how does it relate to our definitions of health, our predispositions to disease and our manifestations of disease?
GROSS: So this leads to exactly what youre doing now, which is cataloging the human micro biome. Youre cataloging what microorganisms live on and in us and what do they do. And this has great implications for health care, for remaining healthy and for treating disease. Do you want to say any more about why you're cataloging the micro biome?
Dr. GORDON: We're trying to identify who's there and whats there. But more importantly, we're trying to understand how these compendium of microbes, how these vast collections, operate as a community, how they are shaped by the habitats in which they live, in turn, how they shape us. And I think that's the principle objective here. It's not simply to create a list, but to understand at the end, how these communities operate in health and in disease, how they contribute to our normal physiology, how they are components of our physiological variations, how they affect our risk for disease, and lastly, could they be a new set of targets, these communities, for personalized medicine.
These microbes have learned a lot about us. We should be humble. We need to go to school and learn the lessons that theyve learned. And some of these lessons may be very important in terms of treating or preventing diseases.
GROSS: So some microorganisms keep us healthy, others are bad guys and make us sick. Give us a dramatic example of a study that was done - an experiment, just to see if transplanting good guy bacteria into a gut could help treat a disease. And there's actually a very specific experiment I'd like you to discuss, if you could, and that had to do with a patient who had a C. difficile, which is a bacterial infection that causes such extreme diarrhea that some elderly people die as a result. And it's an infection that spreads in a lot of nursing homes and hospitals, and is really horrible for people who have it.
Dr. GORDON: Yes. This is a disease that can produce acute illness. It's a disease that in some cases, when treated, comes back again. And as you alluded to, in this particular example, a patient with C. difficile was treated with a microbial community, a gut microbial community from a healthy individual.
GROSS: So how was that done in this particular experiment?
Dr. GORDON: Well, in this particular case, a fecal community was transplanted into a diseased individual's gut and there was a beneficial effect observed over time, reflected in improvement of their symptoms. But let's step back for a moment and ask: to what extent can we attribute different aspects of our physiology to our microbial communities?
If a person has a physiologic state, if they're obese or if they have diseases like inflammatory bowel disease, how much of that disease is attributable to their microbial communities and how could we establish that relationship? How much of their physiological phenotypes - by that I mean certain aspects of their biology - can be transmitted to another individual via their microbial communities?
GROSS: I guess one of the things I find so interesting about this fecal transplant is one, its a fecal transplant. It's so odd to think of using in this case, a spouse's feces or the community of microorganisms in those feces to transplant into the ill person's gut. Its a way of transplanting good guy bacteria instead of using antibiotics to just kill the bad guy bacteria and in the process, kill the good guy bacteria too.
Dr. GORDON: Exactly. Well, first of all, I agree, it evokes a sort of scatologic focus and...
GROSS: Which I see youve been trying to avoid because that's so creepy...
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GROSS: ...to think about it but...
Dr. GORDON: Well, actually, it's also a reflection that most people have this view of our encounters with microbes from the perspective of disease. But that couldnt be farther from the truths. Most of our interactions with microbes are beneficial and are healthy. And here you have an example of a transplantation of a microbial community. Not one organism, because we wouldnt know which one organism to introduce to help cure this recurrent and relapsing and severe disease, but rather a whole ensemble of organisms - a society that has been assembled that functions to promote health in the donor and now is brought to a new place where it can affect the perturbed or disturbed functions of a community, and I think that's quite amazing.
Of course, we have to understand the details, as we talked about earlier, about how that worked, what components of the community invaded, took hold, what their professions or niches were that allowed them to help eradicate this disease. And can we do this, not only in the context of C. difficile, but other diseases where this function, at the level of a microbial community, like metabolic dysfunction, could somehow be cured.
GROSS: If youre just joining us, my guest is Dr. Jeffrey Gordon. He's the director of the Center for Genome Sciences and Systems Biology at Washington University in St. Louis. And what they are doing here is cataloging the human microbe biome - the microorganisms living in or on the human body and considering what impact that has on human health and on human disease.
Let's take a short break here and then well talk some more.
This is FRESH AIR.
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GROSS: My guest is Dr. Jeffrey Gordon. He's the director of the Center for Genome Sciences and Systems Biology at Washington University in St. Louis. And this center is cataloging the human microbe biome - the microorganisms living in or on the human body.
Now youre doing research on the microorganisms in our gut and the relationship they may have to obesity. Tell us a little bit about the experiments that youre actually doing in the lab now with mice. How do you get the mice to have the same kind of microbe biome - the same kind of microorganisms in their gut as humans do?
Dr. GORDON: Well, we started out by comparing mice with mouse gut communities and mice that were obese, either because they had genetic mutations that made them obese or because we fed them diets that were the equivalent of Western diets. And we observed that there were changes in their microbial communities that were associated with obesity. We didnt know whether those changes and who's there and what genes are there in those communities were casually or causally related to obesity. So we did a micro biome transplant experiment.
And let me explain what that involved. We took a set of mice that were lean, we took a set of mice that were obese and transplanted their microbial communities into germ-free recipients. These were mice that were reared under very special circumstances were they were never exposed to microbes during the course of their lives and they received these microbial community transplants when they were adults. And we noted that those mice that received the microbial communities from obese donors gained more fat than those mice that received microbial communities from lean donors.
GROSS: So look into the future five years from now and give us one example that you think is a possible way, and I know this is all hypothetical, but a possible way we might use the knowledge of bacteria to treat or prevent a disease.
Dr. GORDON: I think that very targeted manipulation of microbes in a gut community with very focused antimicrobial therapies. Or, the introduction of very well-equipped bacteria that can digest components of our diet will be a series of approaches that will be used.
Second, I think that there are certain genes that decorate the surfaces of our gut - the lining surfaces of our gut - that are being manipulated by our microbial communities and that we'll see chemical entities, either those made by the microbial communities or those invented by pharmaceutical companies -that may be already invented by pharmaceutical companies - applied to those human genes that are being manipulated by the microbes, either to enhance the effects of the microbes, these genes, or to block the effects of certain microbes on these genes.
GROSS: Well, Dr. Jeffrey Gordon, thank you so much for talking with us.
Dr. GORDON: Thank you for listening and its a pleasure.
GROSS: Dr. Jeffrey Gordon directs the Center for Genome Sciences at Washington University in St. Louis. You can download Podcasts of our show on our website, freshair.npr.org.
I'm Terry Gross.
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