What makes some people slender and others full-figured? Besides diet and genetics, the community of microbes that lives inside us may be partially responsible. New research on twins suggests that lean people harbor bacteria that their obese counterparts don't have. And, given the chance, those bacteria may be able to prevent weight gain. But don’t dig your skinny jeans out of the closet just yet. So far, the work has been done only in mice. What's more, the bacterial takeover requires a healthy, high-fiber diet to work, illustrating the complex relationship between diet, microbes, metabolism, and health.
Our intestines are home to at least 400 species of bacteria, and evidence is building that the balance of microbes in our internal ecosystem has far-reaching effects on health, including brain function and risk of cancer. A study last year showed that transferring gut bacteria between humans reduced insulin resistance, which is linked to obesity.
To explore how microbes differ between obese and lean people, researchers at Washington University in St. Louis took gut bacteria from four pairs of identical and fraternal twins; one sibling in each pair was lean and the other obese. Then they transplanted these microbes into mice that had no intestinal microbes of their own. The mice who got microbes from the lean twins stayed lean, the researchers report today in Science. Those that got microbes from the obese twins increased their body fat by 10% on average, even though they were eating the same amount of food.
What would happen if these two sets of microbes got mixed up in the gut, the researchers wondered. Led by microbiologist Jeffrey Gordon and graduate student Vanessa Ridaura, the team took advantage of one of the rodents' least endearing habits: They eat each other's poop. After letting this happen, the researchers discovered that microbes from the lean twins seemed to be particularly good at taking hold in the gut ecosystems of the mice that started with obesity-associated microbes. And after those bacteria moved in, the mice didn't gain weight. The most invasive species of microbes from the thin animals were in the Bacteroidetes group, which has previously been associated with leanness in mice and humans. The obese mice seemed to have unoccupied niches that the Bacteroidetes could easily move into.
To figure out what the gut bacteria might be doing, the researchers looked for bacterial genes that were active in the two kinds of mice. The heavier mice had higher levels of proteins involved in detoxification and stress responses; the lean mice expressed more genes involved in breaking down dietary fiber.
Diet, it turns out, was key to the impressive properties of the microbes from the lean twins. All the mice in the first round of experiments had been eating chow that was high in fiber and low in fat. The researchers then prepared a mouse-pellet form of an unhealthy human diet, high in fat and low in fiber, and housed svelte and heavy mice together again. They found that, with this diet, the microbes associated with leanness didn't colonize the cagemates’ intestines.
This work was rigorously done and fits in well with earlier findings, including the idea that Bacteroides may protect against weight gain, says Alan Walker, a gut microbiologist at the Wellcome Trust Sanger Institute in the United Kingdom who was not involved in the study. What's new here, he says, is that the researchers began addressing the question of how that protection might work: which species are responsible, what genes they use, and what diet they require.
"This study is an important step toward ultimately answering these questions," says microbiologist Peter Turnbaugh of Harvard University. A valuable result of this work, they both agree, is that it sets up a way to test the effects of microbial therapies on human gut bacteria (even though the bugs are living in a mouse). The authors suggest that a logical next step is to use the animals to measure the effects of particular foods or ingredients on gut ecosystems.
The mouse experiments also provide a way to test fecal transplants, which can cure a potentially fatal intestinal infection in humans and show potential for treating other conditions such as inflammatory bowel disease and obesity. There's a danger inherent in this approach: Transferring human feces into a patient's colon runs the risk of transmitting pathogens as well. Walker and the authors note that a well-tested "next-generation probiotic" consisting of known beneficial microbes delivered as a pill or other therapy could take the place of fresh feces, and this mouse system provides a way to identify the most effective bacteria, the diseases those bacteria can treat, and whether a particular diet is necessary.
"There's a major way to go before you can translate these results to humans," Walker cautions. A weight-loss probiotic isn't a simple next step, as the researchers found when they isolated 39 of the beneficial Bacteroidetes species. The mixture was unable to cause the same effects as mouse poop, possibly because the Bacteroidetes aren't acting alone and more of the microbial players need to be identified.