Here's an alternative explanation for the obesity epidemic: Blame it on bacteria.
A small group of scientists say their research in mice suggests that a large part of the difference between fat people and thin people may come down to the microbes that live in their guts.
The human digestive system is home to between 10 trillion and 100 trillion bacteria -- at least 10 times the number of human cells in the body. ''This makes us more microbe than man," said Dr. Jeffrey Gordon, director of the Center for Genome Sciences at Washington University School of Medicine in St. Louis. In exchange for shelter and a plentiful food supply, these bacteria boost their host's digestion by extracting nutrients from otherwise indigestible food particles.
Gordon believes, though his science isn't there yet, that people with certain communities of gut microbes may get more calories from their food -- and therefore pack on more fat -- than people with a different set of bugs. Manipulating these bacteria by diet or medications may eventually become one approach to fighting obesity, he and others said.
''I have no doubt that 20 years from now we will treat some diseases" -- like obesity -- ''by restoring or enhancing the numbers" of certain microbes, said Dr. David Relman, a microbiologist at Stanford University who is not involved in the obesity research. ''But first, we need to know which are the key organisms and what they do for such treatments to be efficient or permanent."
Although there are products on the market that claim to manipulate the bacteria in the system -- prebiotics that enhance the growth of certain microbes and probiotics like certain yogurts that contain live bacteria -- Relman, Gordon, and others said the research isn't far enough along yet to suggest a specific health benefit from these products.
Gordon's investigations over the past two years have revealed that ''gut bugs," as he calls them, have a huge impact on weight gain in mice. He compared normal mice with guts full of bacteria to a strain of gnotobiotic, or germ-free, mice, which are born without gut microbes and are housed in sterile plastic bubbles. The lab found that while the gnotobiotic mice were able to feast on rodent chow and remain thin, their genetically identical counterparts with bacteria in their guts ate 29 percent less and had 42 percent more body fat. The bacteria made the mice fat.
When the gnotobiotic mice were exposed to bacteria, their guts filled up with microbes and they quickly got fat, reaching the same weight as the other mice in just two weeks.
Perhaps, Gordon mused, he could make fat mice lean by reducing some populations of gut bugs while encouraging others -- and possibly do the same for humans. But first he needed to know whether genetically lean and genetically obese mice each had a characteristic set of gut bugs.
Last August Gordon and postdoctoral researcher Ruth Ley published a study in which they looked at three types of mice, identical except for mutations in what the scientists call the ''obese gene." This gene produces a hormone, leptin, that limits food intake. The first group of mice, which lacked functioning leptin genes, were grossly obese. The other two groups, with one or two functioning leptin genes, were both lean.
The guts of the lean mice, they discovered, were dominated by a type of bacteria called Bacteroidetes, while the guts of the genetically fat mice were dominated by a group called Firmicutes.
That still left open the question of whether specific types of bacteria were contributing to the weight loss or a result of it. To try to answer that, Gordon's lab is implanting specific combinations of microbes into the guts of the germ-free mice to observe the impact on weight gain. He is also investigating whether all genetically obese mice have a characteristic set of gut microbes and whether these results apply to humans.
An individual's gut flora are primarily derived from its mother. In the womb, the fetus is germ-free. It gets its first exposure as it slides through the birth canal. The microbial community continues to expand during suckling and weaning, and the cast of characters is more or less complete by age 2.
The bacteria aren't freeloaders. Bacteroides thetaiotaomicron, for example -- the most populous member of the bacterial community -- produces 240 carbohydrate-busting enzymes that enable it to break down a massive range of plant fibers. Humans, by comparison, have a much more limited toolbox, with fewer than 100 of these enzymes. This ''microbial nation," Gordon explained, allows humans to digest food that evolution hasn't enabled them to digest on their own. Each person's digestive system harbors roughly 550 different phylotypes, or species, of microbe, according to a census Relman published last year. However the three adults Relman studied had very diverse microbial communities -- suggesting that the number of gut microbes probably numbers in the thousands and that the variation from person to person could be enormous.
This suggests ''there won't be a magic bullet for all populations," Relman said. Personalized medicines for complex diseases such as obesity might require matching different microbial cocktails to an individual's genetic backgrounds.
Ultimately, this research and work on human genetics will help researchers develop personalized nutritional recommendations, said Jose Ordovas, director of the Nutrition and Genomics Laboratory at Tufts University.
''We have ignored gut microbes and their contribution for a long time," Ordovas said. ''But we cannot forget we carry much more DNA than our own."