When inoculated with the gut microbes of an obese woman, mice gained substantially more fat than when they were given gut microbes from the woman's identical but lean twin sister.
The finding is just one of the latest in a series of studies to show that the communities of microorganisms that live in our digestive systems -- also known as the microbiome -- may have profound effects on our health. And while there are still many details yet to be understood, the new findings suggest that we may some day be able to prevent or treat obesity by fiddling with the composition of tiny organisms that live inside us.
"Every year for the past 35 to 40 years, the weight of American society has been steadily going up, and we're now about 6 billion pounds overweight as a country," said Ronald Evans, a molecular biologist who studies the impact of the genome on diabetes and heart disease at the Salk Institute in La Jolla, Calif. He was not involved in the new study.
"Maybe the microbiome is a critical part of that," he said. "It would be great if you could take a cultured microbiome in a dish and give it to people and create healthier individuals. This study illustrates the potential and challenges of that, but it's an important step forward."
Although our own genes are generally fixed, each of us carries around the genes embedded inside 100 trillion microorganisms. Those microbes outnumber our own cells by a factor of 10 to one, making us "super-organisms," Evans said, composed of our own genes and the genes of our microbiome.
There are thousands of different kinds of bacteria that can make up the microbiome, and in recent years, studies have revealed that what we eat influences the kinds of microbes that thrive in our guts.
Two recent papers published in the journal Nature, for example, showed that high-fat, high-calorie diets were linked with simple microbiomes that were low in genetic diversity, and people with less diversity in their guts had more inflammation, more insulin-resistance and other signs of metabolic disease. When people switched to a low-fat healthy diet, the diversity in their guts increased.
That raises a chicken-and-egg question. Does becoming overweight change the microbiome? Or do changes in the microbiome drive weight gain?
To tackle that question, a team of researchers collected feces from four pairs of twin sisters that had one lean sibling and one who was obese. Then, they transplanted those feces into mice.
Two weeks later, the team reports today in the journal Science, the mice that got the "bad" microbiome from the obese twin had gained 10 percent more fat than the mice that got the "good" microbiome. Those mice stayed lean.
Diet mattered, too. When the researchers put mice from both groups in the same cage, the "lean" microbes colonized the mice originally given the "obese" microbes and helped protect them from gaining weight. But that only happened when the mice were given healthy food that was low in fat.
This "establishes that microbes can cause obesity -- at least in mice," said Rob Knight, one of the study's co-authors based at the University of Colorado at Boulder. "Additionally, it shows that mice can be protected from obesity by introducing a carefully designed microbial community."
One hope for the future would be a magic pill that would alter the microbiome and treat or prevent weight-gain.
Evans was more cautious about interpreting the results. Ideally, he said, it would be helpful to be able to show the same effects in people, not just in mice.
And there are still plenty of open questions about the feasibility of fecal transplants and the best way to culture microbes.
For now, the new study "definitely implies that changes in the microbiome not only are linked to changes in disease state but may directly contribute to it," Evans said. "It's a step in that direction."