Fat friends: gut-microbe partners bring in more calories.

The collaborative efforts of two common gut microbes could increase the calories that a person extracts from food and stores as fat, a new study in mice suggests.

Trillions of bacteria and archaea--single-celled organisms that resemble bacteria but form another branch of life--occupy the intestines of healthy people and other animals. These microbes provide many benefits to their hosts, such as breaking down nutrients. Scientists have suspected that microbial species change each other's digestive roles, and researchers are now beginning to work out these complex interactions.

To investigate how one human-gut bacterium interacts with the most common human-gut archaeon, microbiologists Jeffrey I. Gordon and Buck S. Samuel of Washington University in St. Louis experimented with mice specially bred and raised to be missing all gut microbes.

The researchers fed some of the mice a solution containing the bacterium Bacteroides thetaiotaomicron and gave other mice a solution containing the archaeon Methanobrevibacter smithii. A third group of animals received both species.

Over the next 2 weeks, all the animals ate sterilized chow rich in polysaccharides, which are sugars that neither mice nor people can digest without the help of certain gut bacteria, including B. thetaiotaomicron. The researchers found that the intestines of mice treated with both microbes had 100 to 1,000 times as many individuals from each species as did the intestines of mice treated with only one species.

The finding suggests that B. thetaiotaomicron and M. smithii somehow benefit each other, says Gordon.

To learn how the microbes boost each other's populations, Gordon and Samuel took samples of the bacteria and archaea several days after the microbes had colonized the mice. Analyses of gene activity showed that in mice with just B. thetaiotaomicron, the bacterium consumed various polysaccharides. However, in the presence of M. smithii, B. thetaiotaomicron focused its appetite on the class of polysaccharides called fructans. Fructan-specific digestion leads the bacteria to produce hydrogen, which fuels M. smithii.

Fructan digestion also creates an abundance of acetate, which mice can digest, Gordon adds. Wondering whether the extra calories from acetate produced extra fat, the researchers X-rayed the mice to measure their fat deposits. Gordon and Samuel report in an upcoming Proceedings of the National Academy of Sciences that mice with both microbes had about 13 percent more fat than mice colonized with just one species did.

The study suggests that the calories that people and other animals take from foods could be directly related to which microbes have colonized their guts. To understand foods' effects on weight, "we have to consider someone's microbial ecology," says Gordon.

If the scientists' reasoning is correct, then manipulating intestinal flora might eventually be used to treat obesity, notes microbiologist Jeremy Nicholson of Imperial College London. However, he adds that because researchers are still investigating the individual functions of the gut's many microbial species, such a treatment might be years or decades away.