Science: Diet-Dependent Microbes in the Gut Can Trigger Obesity


Turnbaugh et al. describe a pipeline where human gut microbial communities and diets are recreated in gnotobiotic mice, and the impact on microbe and host is defined using metagenomics. Background freeze fracture scanning EM images of B. thetaiotaomicron, a well studied human gut microbe, are courtesy of John Heuser, Robyn Roth and Eric Martens.
[Image © Science/AAAS]

Pinpointing obesity triggers in humans is hard because of uncontrollable genetic, cultural, and environmental factors. Recent studies have thrown another element into the mix: the microbiota—a distinct community of microorganisms that reside in the human gut and play an active role in its environment.

This “living organ” is composed of billions of bacteria that provide a variety of valuable functions to its human hosts, such as degrading and promoting the absorption of food that would otherwise be indigestible.

Now a new study by researchers at the Washington University School of Medicine in St. Louis shows that a high-fat, high-sugar diet promotes lasting changes in the gut ecosystem of mice—and those changes contribute to obesity. The results put a spotlight on the human gut microbiota as a new factor to consider in the search to understand and treat obesity.

“We never dine alone: Every time we sit down to eat we are joined by billions of microscopic friends,” said lead author Peter Turnbaugh, formerly a postdoctoral fellow in Jeffery Gordon’s lab at the Washington University’s Center for Genome Sciences.

The Gordon lab group transplanted microbes from human fecal matter into “germ-free” mice bred without any microorganisms in their guts. They found that when mice with human microbiota are fed a high-fat, high-sugar, “Western” diet, a rapid change occurs in the population of bacteria present in the gut, along with a visible increase in body fat; compared to mice fed a low-fat diet.

As further evidence of the important role that the gut microbes play, the researchers also found that simply transplanting the microbiota from the mice on the high-fat diet into a set of germ-free mice caused the new mice to accumulate more body fat, even though they were fed a low-fat diet.

“The most interesting part of the study was the rapid nature of the microbial response to a shift in diet—we found a dramatic change after only a single day,” explained Turnbaugh. “If these findings hold up in human studies, it could mean that the human gut microbiota is more responsive to diet than previously appreciated, and that we may be able to manipulate the abundance of specific microbes through dietary interventions.”

Next, the Gordon lab plans on using “humanized” mice to study gut microbial communities from many diverse human populations, including obese and malnourished individuals. The eventual goal is to better understand the links between diet, energy balance, and the human gut microbiota, with the hopes of someday using interventions to alter the metabolism or function of specific groups of microbes.