by Roger Highfield, Science Editor
December 21, 2006
Microscopic inhabitants of the human gut may make some people prone to being obese, a remarkable finding that may have implications for the treatment of this worldwide epidemic. Although there is no doubt that genetics plays a large part in determining body weight and waist measurements, the increase in prevalence of obesity over the past 25 years cannot be attributed to changes in the human genetic make up.
The availability of inexpensive high-fat foods and the reduction in physical activity are important influences but today an American team raises the intriguing possibility that the trillions of bacteria in the gut also contribute to differences in body weight, suggesting that ways to change this microbial ecology could help to cut weight.
In two studies published in the journal Nature, the scientists report that the relative abundance of two of the most common groups of gut bacteria is altered in both obese humans and mice. By transplanting these communities into mice, the researchers showed that the obese microbial community has an increased capacity to harvest calories from the diet. The human digestive system is home to between 10 trillion and 100 trillion bacteria - at least 10 times the number of human cells in the body. Our gastrointestinal tracts house two dominant groups of beneficial bacteria, the Bacteroidetes and the Firmicutes, which help us to break down otherwise indigestible foods. The relative proportion of Bacteroidetes is lower in obese compared with lean people, Prof Jeffrey Gordon of Washington University School of Medicine, Dr Ruth Ley and colleagues report in Nature. And the proportion increases as weight is lost on low calorie diets, revealing how Bacteroidetes could help weight loss.
In a second study, the team underlines the role of the microbes by reporting that species in obese mice are better at harvesting calories from food - breaking down otherwise indigestible molecules - than those found in their lean littermates. And the effect is transmissible - when 'obese microbes' are transplanted into germ-free mice their total body fat increases more than when 'lean microbes' are transplanted. "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 Prof Gordon. "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, not every snack of a given number of calories may yield the same number for each person. People could extract slightly more or slightly less energy from a serving 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," Prof Gordon says. The Firmicutes include Lactobacillus, Mycoplasma, Bacillus and Clostridium. The slimming Bacteroidetes include Bacteroides, notably Bacteroides thetaiotaomicron.
Many types of polysaccharides pass through the small intestine mostly unchanged because we lack the genes needed to digest them but Bacteroides thetaiotaomicron can break down these nutrients so that the stored calories can be liberated and absorbed. The new work suggests that scientists could manipulate them by diet or drugs to treat or prevent obesity.
But the human gut contains hundreds, and perhaps thousands, of different microbial species, and the functions they perform affect each other and their hosts, so doing this in a controlled way may prove difficult. Although there are already products on the market that claim to manipulate the bacteria in the system, not enough is understood about how to do this reliably.
"This is a potentially revolutionary idea that could change our views of what causes obesity and how we depend on the bacteria that inhabit our gut," commented Prof Randy Seeley of the University of Cincinnati. "But a great deal remains poorly understood."