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May 23, 2007
The Gut's Long Grip
Bacteria in the intestines influence
digestive health and obesity, but a new set of
experiments this suggests even farther-reaching effects. Specifically, they also
affect how fat is digested and deposited in the
liver. The results suggest how an imbalanced gut flora
might alter fat metabolism and contribute to disease.
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 Nestle 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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