Jeffrey Gordon from Washington University
Part of the show Red Wine, Caffeine and Bugs in Your Gut
Chris - Tell us about your study and how you discovered a link between stomach bacteria and weight gain.
Jeffrey - Let me start out with a sobering or inspiring thought depending upon your perspective. Adult humans are composed of ten times more microbes than they are human cells. Now the question is what do these microbes do to us, how do they benefit us, how do they form strategic partnerships with us? We began this study using a good stand in for humans, the laboratory mouse. We took a look at genetically obese mice and their lean litter mates. And found that the principle bacterial groups in the gut, so called Firmicutes and Bacteroidetes, were present in different proportions in the obese, compared to the lean mice.
Chris - Is that just because these animals have been genetically tinkered with to make them fatter?
Jeffrey - The implications are that there may have been a link between the amount of fat and the composition of the microbial community. We did another series of experiments and took the communities from obese mice and started sequencing the genes from those communities. Then compared the gene content of the obese community to the gene content of the lean gut community. Again this is in mice. And we found that the obese mouse community had a greater capacity to break down certain components of our diet that are difficult to digest with our own enzymes.
Chris - So the bacteria are lending their genes to our gut? So the bacteria, by breaking down food we can't normally access are feeding us additional calories.
Jeffrey - Well there's an increased efficiency of breaking down these components of our diet, which are called polysaccharides. These are complex sugars. The idea spawned from these experiments was that perhaps when people sit down with a bowl of cereal in front of them, which are rich in polysaccharides, that some individuals are able to extract more calories than their dining partners, who had a different suite of microbes. So even thought the package labels may say 110 Calories per serving size, that's an absolute value. In the real world, depending upon your gut microbes, you may have slightly more or slightly fewer calories delivered to your body as a result.
Chris - So you've looked in mice and found this relationship, mice that are fatter have a different spectrum of bugs in their gut, they get more energy out of their food, and this might be contributing to weight gain in the mice. But what about in humans, is the same true?
Jeffrey - We've recently taken a group of 12 human volunteers, all obese, and put them on one of two types of low calorie diet. One where fat was restricted, and one where carbohydrates were restricted. And we looked at their gut microbes, before they began this diet, and during the time that they lost weight. And we found that just like in obese mice, these gut microbes that are more abundant in the mice are also more abundant in obese human guts. And those that are diminished are also diminished in obese human gut. And the more diminutive group begins to expand as you lose weight. Interestingly, it's not just one member of these groups that are changed, it's the whole group that shifts in its relative abundance. So there seems to be a dynamic linkage to the amount of adipose tissue you have, and the nature of your gut microbe community.
Chris - Now what happens if you take that spectrum of bugs that live in a fat mouse, and colonise the gut of a mouse with a different community of gut bugs, that's slim? Does it gain weight?
Jeffrey - A very good question. You can raise mice under completely sterile conditions; they're called germ - free animals, to adulthood. And then you can do a microbial community transplant. You can take a microbial community from an obese mouse and transplant into one of these germ-free animals, and observe how much fat they gain over time. And you can do the same thing where the donor is a lean mouse. And just as you imply, the obese gut microbial community is able to direct a greater increase in fat than the lean community. So this characteristic is transmissible. What we don't know is whether some people start out, even before they become obese, with a slightly greater amount of one group, that we call the Firmicutes, and a more diminished amount of the Bacteroidetes. And whether they're predisposed, depending on their diet, to extracting more calories.
Chris - I guess that's what you'll look at next.
Jeffrey - Absolutely. And we have to really understand what these groups of different bacteria bring to the dining room table. It's really part of a larger attempt to understand how these alliances between humans and that our microbial companions benefit us. And whether there are differences in our microbial community structures that impart to each one of us distinctive physiological characteristics.