Many factors play a role in the propensity to gain weight, including genetics, physical activity and the environment, as well as food choices. But a growing body of evidence, much of it accumulated by Dr. Jeffrey I. Gordon of Washington University in St. Louis, shows that bacteria in the gut also play a key role. His findings could lead to new ways to induce weight loss or to prevent weight gain. Humans need bacteria in their gut to help convert otherwise indigestible foods into a form that is digestible. Human intestines contain trillions of bacteria, perhaps 10 of them for every cell in the body. Although hundreds of types of bacteria are present, 90 percent of them fall into two major divisions, or phyla: the Firmicutes and the Bacteroidetes. Previous research had shown that obese mice had higher levels of Firmicutes, while their lean littermates had more Bacteroidetes. Analyzing the genomes of the bacteria, Gordon and graduate student Peter Turnbaugh concluded that the Firmicutes were more efficient at digesting food that the body can't, such as the complex sugars in grains, fruits and vegetables, breaking them down into simple sugars that can be used by the body. Because these bacteria are more efficient, animals that have a higher proportion of Firmicutes convert a higher proportion of ingested food into calories that can be absorbed by the body, making it easier to gain weight. Over the course of a year, for example, a small increase in absorbed calories could lead to significant weight gain, Gordon said. When the researchers transferred bacteria from the guts of obese mice into so-called gnotobiotic mice, which were raised in a sterile environment and had no bacteria in their guts, the mice gained more weight than did those receiving a similar amount of bacteria from lean mice, even though they were fed the same diet. But that was in mice. The question remained whether bacteria in the human gut could do the same thing. In the new research reported Wednesday, Gordon, Turnbaugh and their colleagues found that they could transfer bacteria from human intestines into gnotobiotic mice, creating 'humanized' mice that in themselves may prove to be a valuable research tool. The gnotobiotic mice were fed a low-fat, plant-rich diet in the weeks before the bacteria were transplanted and for a month afterward. Analyzing the genomes of the bacteria, the team concluded that the bacterial colony in the mice was virtually identical to that of the human donor. After the bacteria were transplanted from a lean human donor, the colonies in the mice had a high proportion of Bacteroidetes and a low proportion of Firmicutes. But within 24 hours after the mice were switched to a high-sugar, high-fat diet, the proportions of the two phyla were reversed. With time, the mice also grew fatter than their littermates who did not receive the human bacteria. Furthermore, when the bacteria from these obese mice was transplanted into other gnotobiotic mice, those animals gained weight, even though they were kept on a low-fat diet. These findings suggest that the bacterial colonies can be passed from generation to generation, providing an explanation beyond genetics for why obesity runs in families. The team is now studying bacterial colonies from malnourished children to see if the bacterial population can be altered to increase the children's ability to use food. 