November 12, 2009
A high-fat, high-sugar diet can quickly and dramatically change the population of microbes living in the digestive tract, according to a new study of human gut bugs transplanted into mice.
Trillions of microbes live inside the human gut, and one of their functions is to process parts of foods that we can't digest on our own. Recent studies have suggested that certain populations of microbes may be associated with obesity.
"The energetic and nutrient value of food may not be an absolute term, but one that is modified in part by the microbes that live in our gut — who's there in this community, how they operate, and how they operate in relationship to what we are eating," says Jeffrey Gordon of Washington University School of Medicine in St. Louis, Mo.
He and other scientists are eager to start doing experiments to see what happens if the gut populations are modified by changes in diet, antibiotics, or dietary supplements. To make such experiments possible, Gordon has been working with colleagues to take gut microbes from human feces and transplant them into the intestinal tracts of previously germ-free mice.
A Gut Bacteria 'Census'
Using powerful DNA sequencing tools that allow them to take a "census" of the gut bugs without having to culture them, Gordon's team then showed that this kind of microbe transplant is successful. The mice end up with a collection of gut microbes that mimic the populations found in the original human sample.
Then the team explored what would happen to these microbes if mice were switched from their standard low-fat, plant-rich mouse chow to a diet that was high in fat and sugar.
They found that in less than 24 hours the gut's microbial populations changed abruptly, according to a study in the journal Science Translational Medicine.
"We were quite amazed that the community really restructured itself in terms of the proportional representation of different bacterial species, the proportional representation of genes with different functions, in a very short period of time," says Gordon. "Certain members of that society of microbes became very dominant, and certain members became more diminutive."
And when this new collection of human microbes was transplanted into germ-free mice, the mice gained an increased amount of fat tissue even when fed low-fat diets, compared to mice that got human microbes from mice fed low-fat diets.
That was the biggest surprise for John Mekalanos, chairman of the department of microbiology and molecular genetics at Harvard Medical School, who co-wrote a commentary that appeared with the research report. "What it really suggests is that our biota really shape the way we respond to food," Mekalanos says.
DNA Sequencing Tracking Diet Changes
While other studies have looked at putting human gut microbes into animal models before, this is the first to use DNA sequencing tools to really track changes in response to diet, says Mekalanos. "Using these state-of-the-art new-generation sequencing techniques is what makes this paper particularly powerful," he says, adding that this type of tracking could eventually identify important microbial players that could be targets for future experiments on trying to treat obesity by modifying gut bacteria.
No one currently knows if gut bugs are an important contributor to human obesity or if targeting them could lead to novel therapies. But Mekalanos says that this new study makes it more likely that scientists will be able to explore those possibilities "because one needs a pre-clinical model before one devises complicated, expensive human subjects trials."
The work is just the beginning of what Gordon hopes will be a whole slew of experiments to tease out how diet and microbes interact to affect nutrition and weight gain.
"Once we have analyzed a human specimen, we can actually test its functions in a living organism under highly controlled conditions," Gordon says. "And we can do that with participants — volunteers — who live in different cultural contexts, with different lifestyles, different diets, to recapitulate their gut ecosystems and their diets."
That will allow researchers "to be able to look at this intimate relationship between our microbial selves and our human cellular selves," Gordon says.
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