reposted from: Nature Podcast: 21 December 2006
from Nature Podcast / Original audio source
Nature Video: http://www.nature.com/nature/videoarchive/gutmicrobes/index.html
my highlights / edits
In "Conclusion" (3rd video) Jeff Gordan says: "The study of the coevolution of microbes with human cells may help to treat obesity. Which human genes are manipulated by microbes? The number of calories in food is determined in the lab but the total caloric yield may differ between individuals depending on the ratio of Bacteroidetes and Firmicutes.
This is a transcript of the 21 December edition of the weekly Nature Podcast. Audio files for the current show and archive episodes can be accessed from the Nature Podcast index page (http://www.nature.com/nature/podcast), which also contains details on how to subscribe to the Nature Podcast for FREE, and has troubleshooting top-tips. Send us your feedback to mailto:podcast@nature.com
Transcript reposted: http://www.nature.com/nature/podcast/v444/n7122/nature-2006-12-21.htmlChris Smith: This week, should we think of ourselves as passengers in our own bodies? Well, Jeff Gordon says we should.
Jeff Gordon: A human being is not composed only of human cells. In fact, as adults we contain ten times more microbial cells on our body surfaces than human cells.
Chris Smith: And those very same bugs make a huge difference to whether we're fat or thin;
Hello, Merry Christmas, I'm Chris Smith, welcome to this week's show. First up, who would have thought that bacteria living in your gut could make a big difference to your body weight? Here's Jeff Gordon and his team, Peter Turnbaugh and Ruth Ley who've found that a bulging waistline in mice and humans is associated with a big change in intestinal flora. Nature 444, 1009–1010 (21 December 2006) ; Nature 444, 1022–1023 (28 December 2006) ; Nature 444, 1027–131 (21 December 2006)
Jeff Gordon: We're very interested in the alliances between microbes in humans. A human being is not composed only of human cells. In fact, as adults we contain ten times more microbial cells on our body surfaces than human cells. These partnerships are mutually beneficial. We're very interested in the role of microbes in our gut and one of the attributes that they provide is the capacity to digest otherwise indigestible components of our diet. So the question we had here was do the microbes in our gut influence our energy balance?
Chris Smith: So how did you try and explore that?
Jeff Gordon: We started out with mice and looked at the microbial communities of obese mice. They're obese because they had a genetic mutation that caused them to reliably develop obesity while they were young adults, and compared their community structure to their litter mates who didn't have this mutation and therefore were lean.
Chris Smith: So, Peter Turnbaugh, you're the lead author on this paper, when you actually did this, what did you find?
Peter Turnbaugh: We were able to take advantage of really the revolution that's going on in sequencing technology and so here at Wash U we have the genome sequencing centre, we were able to directly isolate DNA from the mouse gut and take that DNA and use them high throughput shotgun sequencing techniques to try to look at what genes were present in the bacterial community of obese mice and what we found was that there seemed to be more genes in the obese community for harvesting energy from the diet, so breaking down complex sugars that we might eat that the human or the mouse can't normally digest.
Chris Smith: So these guys have got a richer microbial flora effectively?
Peter Turnbaugh: First, originally, when we looked at who's there, we saw that there's two major groups of bacteria, the Firmicutes and the Bacteroidetes, and we saw them in the obese mouse, there was a shift in the relative abundance of these two groups so there were more Firmicutes and less Bacteroidetes.
(From Wikipedia: Researcher Jeffery Gordon and his colleagues found that obese humans and mice had a lower percentage of a family of bacteria called Bacteroidetes and more Firmicutes. But they are not sure if Firmicutes cause obesity or if people who are obese grow more of that type of bacteria.)
Chris Smith: Is the trait transmissible, in other words, can you take that different spectrum and confer it upon another animal and make that animal gain weight because that surely is the way to prove wholeheartedly that this is underlining why they're so fat?
Peter Turnbaugh: Right, exactly, so what we were able to do is harvest the microbial community from an obese mouse, or a lean mouse, and then directly colonize germ-free mice with either the obese flora or the lean flora and what we saw was the mice that were exposed to the microbes from an obese mouse actually gained more fat over the course of the experiment than the mice that were given lean microbial community.
Chris Smith: So that's mice, but actually happens if you look in humans who are too fat, are they, too, carrying an abnormal spectrum of bacteria in their intestines? Ruth Ley is the first author on a second paper which sits next to this one in this week's Nature. Ruth, what did you find in humans?
Ruth Ley: We found that the obese humans did actually have exactly the same shift in their ratio of Firmicutes to Bacteroidetes that we'd seen in the mice.
Chris Smith: How did you actually do the study? Can you tell us a bit about that?
Ruth Ley: We had 12 subjects that were randomly assigned to two different diets, one was a fat restricted diet and the other one was a low calorie diet and these people were on a diet for a year and we collected a stool sample from them before they started the diet and then three times over the course of the year, and just using the same techniques we used for the mice, we extracted DNA from their stool and we sequenced the 16 S genes for the bacteria, which was the one that tells you what kinds of bacteria are present. So we generated a very large amount of sequence for this kind of study and from that we were able to see that first of all before the diet the obese people had a skewed ratio of Firmicutes to Bacteroidetes compared to lean people so we also had some lean controls and then as they lost weight, the amount of Bacteroidetes increased and began to resemble what you would see in a normal lean person, and the amount of the increase was proportional to the amount of fat that they actually lost over time.
Chris Smith: So what do you think is going on? Why should just losing weight change the bugs that you have growing in your intestine?
Ruth Ley: Well, that's a mystery at the moment. We know that there's some kind of link, some sort of dynamic linkage between the fat that's carried on the body, we know that fat cells produce hormones and there could be some signaling between the adipose tissue in the body and the kinds of bugs that are in the intestine but at this point we don't understand the mechanism.
Chris Smith: Ruth, thanks, very much. Back to Jeffrey Gordon, Jeffrey, what are the implications of what you found?
Jeffrey Gordon: Well, surely a key element that determines the amount of fat that we store in our bodies is the amount of energy that we consume and the amount of energy that we expend through exercise and work. What this study shows is that there's also a microbial component to determining how much adipose tissue you might have and that they microbes in the gut are part of the equation that affects predisposition to, or the patho-physiology of obesity.
Chris Smith: So now you can blame your gut bacteria as well as a slow metabolism for the extra stone or two that you're carrying around your middle. That was Jeff Gordon, Peter Turnbaugh and Ruth Ley. They're all from Washington University in St Louis and they found that being overweight is associated with a big shift in the types of bacteria found living in our intestines.
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