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Gut infections keep mice lean

Bacteria can invade one rodent from another, preventing both from getting fat

fat and skinny mouse

MICROBE DIET  Mice fed microbes from obese people tend to gain fat. Microbes from lean people protect mice from excessive weight gain, even when animals eat a high-fat, low-fiber diet.

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Skinniness could be contagious. Gut bacteria from thin people can invade the intestines of mice carrying microbes from obese people. And these invaders can keep mice from getting tubby, researchers report in the Sept. 6 Science.

“It’s very surprising,” says molecular microbiologist Andreas Schwiertz of the University of Giessen in Germany, who was not involved in the work. “It’s like a beneficial infection.”

But the benefits come with a catch. The invading microbes drop in and get to work only when mice eat healthy food. Even fat-blocking bacteria can’t fight a bad diet, suggests study leader Jeffrey Gordon, a microbiologist at Washington University in St. Louis.

In recent years, researchers have collected clues that suggest that gut microbes can tweak people’s metabolism. 

Fat and thin people have different microbes teeming in their intestines, for example. And normal-weight mice given microbes from obese mice pack on extra fat, says coauthor Vanessa Ridaura, also of Washington University.

These and other hints have led researchers to experiment with fecal transplants to flush out bad gut microbes and dump in good ones. The transplants can clear up diarrhea and may even help some obese people regain insulin sensitivity. But feces can house dangerous microbes as well as friendly ones.

“We want to make therapies that are more standardized — and more appealing,” says gastroenterologist Josbert Keller of the Haga Teaching Hospital in The Hague, Netherlands.

Scientists are trying to pinpoint helpful gut microbes and figure out how diet guides their role in metabolism. Gordon, Ridaura and colleagues transplanted fecal microbes from obese and lean human twins into mice lacking gut bacteria of their own. Within two weeks, mice that received bacteria from obese people started to put on fat. Mice given bacteria from lean people stayed slim.

Next, the researchers wondered if the microbes could travel between animals and stake out new territory. So the team housed together mice carrying microbes from lean people with mice carrying microbes from obese people. “We called it ‘The battle of the microbiota,’” Gordon says.

Microbes from lean people won: The organisms claimed space in the guts of mice carrying microbes from obese people. What’s more, the invaders kept their new hosts from putting on weight.

The findings sparked a question about humans. If microbes from thin people can jump between animals and prevent pudginess, Gordon asks, “Why isn’t there an epidemic of leanness? The answer is diet, diet, diet.”

Gordon’s team drew that conclusion after repeating the microbiota battle, this time feeding both types of mice a high-fat, low-fiber diet based on American eating habits.

On this diet, lean-people microbes seemed to protect mice from getting chubby: Mice with these bacteria gained less weight than did mice with obesity microbes. But when researchers caged the two types of mice together, lean microbes were no longer able to invade the guts of mice carrying obesity microbes. And without these invaders, mice couldn’t stave off fat gain.

The findings underscore the gut microbiota’s important but limited role in metabolism, Gordon says. “It’s not the only cause of obesity, but it is a contributor.” And a bad diet can tip the scales, thwarting helpful bacteria from accessing the gut.

Now the team is looking into adding microbes to diets to promote health and possibly even repair poor gut bacterial communities. The team identified one group of invading microbes called Bacteroidetes that could help protect against obesity. Gut microbes such as these, Gordon says, could be the next generation of probiotics -- bacteria people consume to improve their health.

“You will never be able to eat everything you want and compensate with fecal transplants or probiotics,” Keller says. “But it’s very difficult for obese people to lose weight with a normal diet, so we need other therapies to support them.”

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