Certain gut flora affect obesity risk

http://www.washingtonpost.com/wp-dyn...001271_pf.html

Research Links Obesity to Mix of Bacteria in Digestive Tract

by Rob Stein, Staff Writer
Washington Post
Thursday, December 21, 2006; A12

Obese people have a distinctive mix of bacteria in their digestive
systems that seems to make them prone to gaining weight, a startling
discovery that could lead to new ways to fight the obesity epidemic,
researchers reported yesterday.

Obese people have more digestive microbes that are especially efficient
at extracting calories from food, the researchers said, and the
proportion of these super-digesting organisms ebbs as the people lose
weight. Moreover, when the scientists transplanted these bacteria from
obese mice into lean mice, the thin animals start getting fat. This
provides more support for the provocative theory that the bacteria that

populate the intestine play an important role in regulating weight.

"There appears to be a link between obesity and the type of bugs in
your gut," said Jeffrey I. Gordon of Washington University School of
Medicine in St. Louis, who led the series of experiments being
published in today's issue of the journal Nature. "The difference in
the structure of microbial ecology of our gut may set us up for
susceptibility to obesity."

Gordon and his colleagues stressed that more work is needed to explore
the findings. And they cautioned against trying to manipulate "gut
flora" with antibiotics or microbial "probiotic" pills sold in
health-food stores. But if the findings are confirmed and better
understood, they could lead to profound new insights into one of the
nation's biggest health problems, the researchers said.

"In the future, we could potentially manipulate the structure and
function of these microbial societies as a new approach toward
preventing and treating obesity," Gordon said.

The findings produced enthusiasm and caution from other researchers.
Some praised the work for possibly offering a long-sought alternative
explanation for the obesity epidemic. Perhaps some change, such as a
food additive or antibiotic use, has caused a fundamental shift in gut
flora, making it easier for many people to gain weight.

"This is very exciting," said Barbara Corkey, an obesity researcher at
Boston University. "We don't know why the obesity epidemic is
happening. People say it's because of gluttony and sloth. I think there
must be something else. It's exciting to see some work being done on
alternative explanations."

Others suspect that if gut microbes do play a role, it is a minor one.

"This is extremely interesting," said Hans-Rudolf Berthoud of the
Pennington Biomedical Research Center in Baton Rouge. "But lifestyle
and the environment are still the major factors in the obesity
epidemic."

On a broader level, the findings highlight the symbiotic relationship
humans maintain with the trillions of microorganisms that populate our
bodies, Gordon and others said.

"This strengthens the notion that the indigenous organisms in the human
body are probably intimately involved in our health," said David A.
Relman of Stanford University. "The ways they are involved remain
unclear, but this underscores the idea that it behooves us to figure it
out."

Scientists have long known that the human body is teeming with germs,
primarily bacteria, which cover the skin and inhabit every orifice. By
some estimates only one out of every 10 cells in the human body is
human. These organisms perform a host of functions, especially in the
digestive tract, where they help digest food.

"There's growing interest in the idea that humans are more than just
human cells," said Martin Jack Blaser of New York University. "These
cells are not just passengers. They are part of the human metabolism."

To explore the role of the organisms in weight regulation, Gordon's
team first compared the gut flora of 12 obese people to lean subjects'.
The obese tended to have a significantly greater proportion of one of
the two main types of bacteria found in the gut, known as Firmicutes,
than the other, known as Bacteroidetes.

Next, the researchers spent a year meticulously measuring the gut flora
of the obese volunteers as they tried to lose weight by eating
low-calorie diets that restricted either their fat or carbohydrate
intake. As volunteers lost weight, the proportion of Firmicutes in
their digestive tracts fell and the proportion of Bacteroidetes rose,
the researchers found.

When the researchers conducted detailed molecular analyses of the two
types of bacteria in the laboratory, they discovered the Firmicutes
were much better at extracting calories from food.

Moreover, when the researchers examined the gut flora of obese
laboratory mice, they found a similar pattern in their ratios of
Firmicutes to Bacteroidetes. And when researchers transferred gut flora
from obese mice to mice devoid of gut flora, the recipient animals
tended to gain weight, confirming that the pattern was associated with
weight gain.

"This attribute of being able to harvest and store more energy appeared
to be transmissible," Gordon said. "For the first time, we see that
there is a correlation between the microbial gut ecology and the obese
state."

Among other things, the findings could help explain why it becomes
harder and harder to lose weight as people get fat, Gordon said.

"That's part of the pathology of obesity. When you shift the amount of
fat tissue, the amount of energy you can harvest becomes somewhat
greater, and that's going to fuel the obese state," he said.

The researchers acknowledged that the difference in the number of
calories extracted by the microbes is relatively small. But over time
even a small differential could be significant, they said.

Many questions remain, however. It is unclear what determines the
make-up of a person's gut flora. It might be the microbes they pick up
from their mothers; it might be their exposure to antibiotics. It is
also unclear how fat tissue and gut flora might affect one another, and
whether the change in gut bacteria causes or is a result of the weight
loss.

Despite those and other questions, scientists said the findings are
sure to inspire more investigation.

"They open up a completely new hypothesis," said Randy Seeley, an
obesity researcher at the University of Cincinnati who wrote a
commentary accompanying the research. "There are a lot of hurdles here
that we have to deal with in terms of our basic understanding. But it's
fascinating."