Scientist - News - 10-12-2009:

The gut reflects what we eat
Beintema, Nienke

Interactions between our gut microbiota, diet and weight are more intimate than previously assumed. Peter Turnbaugh and his colleagues made some surprising discoveries in their experiments with 'humanized' mice.

If you switch from a healthy, low-fat diet to a high-fat 'Western' diet, your gut microbiota may change within a day. These changes are also reflected in the gene expression of the gut bacteria, as well as in their metabolic functioning. That is the conclusion of a recent article in Science Translational Medicine (11 November 2009) by Peter Turnbaugh, Jeffrey Gordon and colleagues. Turnbaugh, a microbiologist now at Harvard University, was one of the keynote speakers at the Gut Day 2009, held last November in The Netherlands.

Humanized mice
Germ-free mice, as the paper explains, are a useful tool to provide information about the human gut microbiota. These mice are born and raised in a sterile environment, and lack any gut microbes. Previous research has shown that these mice are much leaner than their 'normal' conspecifics, which has led scientists to hypothesize that the gut microbiota plays an important role in our metabolism. Gut bacteria allow us to make optimal use of the nutrients that we consume and affect various processes in our body. In fact, if you transplant the gut microbiota of an obese mouse into a germ-free mouse, it will gain more total body fat than if you'd give it the gut microbiota from a lean mouse. These data were published in Nature in 2006.
In their most recent experiment, Turnbaugh and his colleagues created so-called 'humanized' mice: they transplanted human gut microbiota into germ-free mice. "By raising these mice in isolation, we created multiple generations of humanized mice," says Turnbaugh. "This allowed us to conduct some controlled diet experiments that would be nearly impossible with people."

Transmissible
Earlier experiments in humans had shown a correlation between changes in diet, body weight, and a shift in the structure of the bacterial community. "On one hand this is quite frightening," says Turnbaugh, "but it is also potentially interesting: how does our gut microbiota affect our body weight? And can diet, through its impact on our microbiota, really be a key factor in certain diseases?"
The American microbiologists used humanized mice to study the impact of a diet change on gut microbiota and metabolism. They used genetic sequencing techniques to determine the relative abundance of certain groups of bacteria when the mice were eating a healthy, low-fat diet and when they switched to a high--fat, high-sugar diet — a 'Western diet', as Turnbaugh calls it. "A significant shift in the gut microbiota occurred within a day," notes Turnbaugh. "Now we want to interpret these genetic changes in terms of their functional consequences."
In any case, the researchers found that humanized mice that were fed the unhealthy diet had increased adiposity, and, in line with the group's earlier experiments, this trait turned out to be transmissible via microbiota transplantation.

Social implications
Is the opposite true as well? Can we make obese mice lean by giving them the gut microbiota of lean conspecifics? "We performed cross experiments with mice on both diets as donors of gut microbiota, and mice on both diets as recipients," says Turnbaugh. "These experiments showed that current diet has a much larger influence on the composition of the gut microbiota than colonization history. The transplanted gut microbiota adapts to the diet of its new owner within a day, and the 'signature' of the microbiota of the donor is gone within a week."
Turnbaugh's colleague Jeffrey Gordon is collaborating with colleagues around the world to make connections between their work in mice and the ongoing efforts to study the human microbiome. Together they hope to address the social and clinical implications of the recent findings. Can we help obese people to lose weight by altering their gut microbiota? Can we address certain diseases by targeting the gut microbiota? "Such applications are still far away," Turnbaugh notes. "For the time being, our group will be looking into ways to use humanized mice to answer some of the many remaining questions."
Does Turnbaugh himself still dare to eat hamburgers and fries, in view of his own research findings? "I seem to have good microbes," he laughs. "I am lucky enough to be a very skinny person, so I am not too worried."

More information:
Article in Science Translational Medicine (November 2009)
Earlier article by the same research group in Nature (December 2006)