School of Medicine researchers have found a link between obesity and the microbial communities living in our guts.
The findings indicate that our gut microbes are biomarkers, mediators and potential therapeutic targets in the war against the worldwide obesity epidemic.
In two studies published last month in the journal Nature, the scientists report that the relative abundance of two of the most common groups of gut bacteria is altered in obese humans and mice. By sequencing the genes in gut microbial communities of obese and lean mice and by observing the effects of transplanting these communities into germ-free mice, the researchers showed that the obese microbial community has an increased capacity to harvest calories from the diet.
“The amount of calories you consume by eating and the amount of calories you expend by exercising are key determinants of your tendency to be obese or lean,” said lead investigator Jeffrey I. Gordon, M.D., director of the Center for Genome Sciences and the Dr. Robert J. Glaser Distinguished University Professor of Molecular Biology and Pharmacology. “Our studies imply that differences in our gut microbial ecology may determine how many calories we are able to extract and absorb from our diet and deposit in our fat cells.”
That is, the same bowl of cereal may not yield the same number of calories for each person depending upon their collection of gut microbes. “The differences don’t have to be great, but over the course of a year the effects can add up,” Gordon said.
Trillions of friendly microbes reside in the intestine, where they help digest food that the body can’t on its own, such as the complex sugars found in grains, fruits and vegetables. As part of the digestive process, the microbes break down nutrients to extract calories that can be stored as fat.
The researchers focused on two major groups of bacteria — the Bacteroidetes and the Firmicutes — that together make up more than 90 percent of microbes found in the intestines of mice and humans. In an earlier study, they compared genetically obese mice and their lean littermates. The obese mice had 50 percent fewer Bacteroidetes and proportionately more Firmicutes. Moreover, the differences were not due to a bloom of one species in the Firmicutes or a diminution of a single or a few species of Bacteroidetes: virtually all members of each group were altered.
In one of the Nature articles, Ruth Ley, Ph.D., a microbial ecologist in Gordon’s group, reports on her investigation into whether these findings were true among obese humans. She followed 12 obese patients at a WUSTL weight loss clinic for a one-year period. Half the patients were on a low-calorie, low-fat diet, and half were on a low-calorie, low-carbohydrate diet.
At the outset of the study, the obese patients had the same type of depletion of Bacteroidetes and relative enhancement of Firmicutes as the obese mice. As the patients lost weight, the abundance of the Bacteroidetes increased and the abundance of Firmicutes decreased, irrespective of the diet they were on. Moreover, the entire group of Bacteroidetes increased as patients lost weight.
In a companion paper in the same journal, Peter Turnbaugh, a doctoral student in Gordon’s lab, compared the genes present in the gut microbial communities of the obese and lean mice using the newest generation of massively parallel DNA sequencers.
The results of these comparative metagenomic studies revealed that the obese animals’ microbial community genome had a greater capacity to digest polysaccharides, or complex carbohydrates. By transferring the gut microbial communities of obese and lean mice to germ-free mice, he confirmed that the obese microbial community prompted a significantly greater gain in fat in the recipients.
These studies raise a number of questions, according to Gordon. “Are some adults predisposed to obesity because they ‘start out’ with fewer Bacteroidetes and more Firmicutes in their guts?” he asked. “Can features of a reduced-Bacteroidetes Firmicutes-enriched microbial community become part of our definition of an obese state or a diagnostic marker for an increased risk for obesity?”