Bacteria balance.
In the microvilli (green) of the gut, manipulating the types of microbes (yellow) affects the breakdown of fats.

Credit: David M. Phillips/The Population Council/Photo Researchers Inc.

The Gut's Long Grip

By Dan Ferber
ScienceNOW Daily News
23 May 2007

Human intestines harbor hundreds of species of bacteria, some 100 trillion bacteria in all, which make us--if you just count cells--only about 10% human. Biologists have long been interested in what all those bugs are doing in our bodies. Late last year, one team showed that obese people play host to a somewhat different set of bacterial species than people of normal weight. Other experiments suggest that gut microbes play important roles in insulin resistance, which can lead to type 2 diabetes, and in fatty liver disease, a cause of serious liver damage.

To get a more global view of how microbes might alter metabolism, biochemist Jeremy Nicholson of Imperial College London and colleagues at the Nestlé Research Center in Lausanne, Switzerland, compared the health of nine mice with normal microbial flora in their gut with seven mice whose flora were replaced by gut microbes from the feces of a 3-week old human infant. Four weeks later, the researchers measured levels of dozens of biochemical compounds in each mouse's urine, blood, liver, and small intestine.

They focused on compounds called bile acids; the liver makes six varieties, which then travel to the small intestine to dissolve and help take up ingested fats. Bile acids also travel back to the liver and regulate cholesterol metabolism and other endocrine functions. But different gut microbes can modify the structure of bile acids in different ways, adding or snipping off various parts of the molecules, which would presumably alter their fat-dissolving abilities, Nicholson says. The researchers identified 17 variants of bile acid in all in the intestine, some of which fell into one of two chemical classes. The mice with the human microflora had proportionally more of one class of bile acid and less of the other. The researchers also found that the two types of mice had significantly different levels of metabolites in the urine, blood and liver, the researchers reported online this week in Molecular Systems Biology. That suggested that gut microbes may affect metabolism more broadly than thought.

The results are the first to provide a detailed analysis how gut bugs shift the balance of metabolites present, says medical microbiologist David Relman of Stanford University. They also mean, he adds, that altering gut microflora "has far-reaching physiological consequences" for the host animal. Indeed, mice with the human microbes also had more LDL, or bad cholesterol, in the liver and less of a molecule called glutathione, a natural antioxidant that helps prevent tissue damage. Major changes to gut flora like this, Nicholson argues, could predispose the body toward disease.

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