Normally, the immune system and gut bacteria maintain a kind of peace, Gewirtz says. But the mutant mice in this experiment were not normal: They lacked a protein needed to keep bacteria in the intestine where they belong, and out of the bloodstream. In these mice, gut bacteria leak out of the intestines and cause inflammation as the immune system responds to the intruders.
This, in turn, led to a sort of "pre-diabetes" condition in the mice — and by the time they were 20 weeks old, they weighed approximately 5 grams more than normal animals.
Gewirtz's team took the bacteria from the fattened mice and transplanted them into sterile, nonmutant mice. These mice then gained weight. Again, it seemed like just having the wrong bacteria can pack on the pounds.
Scientists have plenty of data that gut bacteria affect weight in mice, but their understanding of the effects in humans remains hazy. For example, not all human studies have shown that firmicutes go hand-in-hand with obesity in people, cautions Margaret Zupancic, a microbial genomicist at the University of Maryland School of Medicine in Baltimore.
In part, that is because it's much more difficult to study people in a carefully controlled way. People, after all, are out and about in the world and have a variety of food and exercise regimes, unlike genetically similar mice living in identical cages eating identical mouse chow.
Another fact hampering scientific study is that intestinal bacteria are difficult to grow in a laboratory setting. Thus, scientists must study the entire community from stool samples and try their best to figure out from those which bacteria serve specific functions.
To get a better handle on the human situation, Zupancic and others are now working with people in a variety of settings, collecting stool samples to further analyze the human gut community and how it interacts with our genetics and lifestyles.
If certain bacterial communities do cause obesity in people, replacing the bad bacteria with the good ones seems like a possible route to weight loss. The idea is not wholly unprecedented. Doctors occasionally treat debilitating diarrhea with a transplant of bacteria from healthy stool, for example. And there is certainly evidence that products called probiotics (see the sidebar) may improve health via a spoonful or swig of bacteria-laden foods. Even simply changing your diet might sway the bacterial community in a different direction, Ley says.
Gewirtz says that someday it might be possible to swap obesity-linked bacteria for skinny-jean microbes. But scientists caution that a nice bacterial cocktail is not the next big weight-loss drink.
For one thing, they don't yet know what bacteria to use if they were to try and concoct such a drink. It is difficult to sort out the relationships between all the factors that lead to obesity, including diet, exercise, genetics — and now, possibly, bacterial inhabitants.
And then, for a bacterial-replacement therapy to really work, doctors would first need a way to get rid of less desirable bacteria already in residence in someone's gastrointestinal tract. The right combination of antibiotics might do the job, Gewirtz says, but there are no well-defined methods for creating such a treatment.
Some companies, meanwhile, already are claiming that the right probiotics can slim you down. This month, researchers from the Japanese company Snow Brand Milk Products reported that people who drank a probiotic milk drink for 12 weeks lost weight. For their study, published in the European Journal of Clinical Nutrition, they offered the probiotic drink or a bacteria-free concoction to 87 people. The subjects were slightly heavy, with an average BMI (body mass index) of 24.2. (A BMI of 25 and above is considered to be overweight.)
Over the course of the study, people drinking the probiotic lost an average of 1.5% of their BMI and, on average, 1.4% of their body weight.
That's about 2 pounds for a 150-pound person.