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A way to bypass gastric bypass? Altering gut microbes may be the key

Doctors perform gastric bypass surgery.

John Ulan/The Globe and Mail

Gastric-bypass surgery is often considered an operation of last resort for severely obese patients who can't seem to lose weight any other way.

But a new study suggests the significant weight loss that is achieved through the surgery might be partly the result of a change in the gut microbes that play a key role in the digestive process. If the microbes can be altered through another means, it may reduce the need for the invasive operation.

"I like to call it bypassing the bypass," said one of the researchers, Dr. Lee Kaplan, director of the Obesity, Metabolism and Nutrition Institute at Massachusetts General Hospital.

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During a gastric bypass, considered the gold standard of weight-loss operations, the size of the stomach is altered with surgical staples to create a smaller pouch for food, and the connection to the small intestine is changed. When the surgery was first introduced decades ago, doctors originally believed the procedure worked because patients tend to eat less, and fewer nutrients are absorbed through the gastrointestinal tract.

Over the years, researchers have noticed the operation changes the body in many ways. In particular, the composition of gut microbes – known as the microbiota – is transformed. Some types of bacteria increase in number, while others decline.

Researchers aren't sure why the microbiota is altered, but some have speculated the changes could affect overall weight. After all, the billions of bacteria in the gut help break down food so the nutrients can be absorbed by the body. They also create compounds that regulate energy balance and fat storage.

To investigate the changes in the microbiota, the U.S. research team performed the equivalent of a bypass surgery on overweight laboratory mice. As expected, the obese rodents that underwent surgery lost weight. The researchers also noticed the surgery was followed by a rapid change in gut microbes.

In the next phase of the experiment, the researchers transferred these altered gut microbes into mice that had been raised in sterile conditions and lacked microbiota of their own. The transplanted microbes spread in the guts of the mice, which then began to lose weight.

"Simply by colonizing mice with the altered microbial community, the mice were able to maintain a lower body weight – about 20 per cent as much as they would if they underwent surgery," Dr. Peter Turnbaugh, one of the researchers at Harvard's Center for Systems Biology, said in a statement. He added the mice might have lost even more weight if they had been put on a high-fat, high-sugar diet first to fatten them up. The mice were thin so they had little weight to lose.

Still, the findings, published Wednesday in the journal Science Translational Medicine, clearly show the microbes are at least partly responsible for the weight loss that accompanies gastric bypass surgery. "If we really understand how this works, we could accomplish the same thing without surgery," added Kaplan.

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"This opens up a whole new way of controlling fat and weight," he added. "But this is the first step in a long process. We are not going to suddenly wake up tomorrow morning and see new bacterial transfer therapies for obesity."

Indeed, the researchers still have much to learn. They don't know how the microbes are contributing to weight loss, although they have some theories. Kaplan speculated that surgery increases the type of microbes that produce signalling molecules that can either stimulate energy expenditure or inhibit the body from storing excess calories as fat.

The researchers face major challenges: It may not be easy to significantly alter the composition of the microbiota in the desired way. The experiment used sterile mice that were easy to colonize by the new microbes. "Of course, there are no germ-free humans," said Kaplan. A person's existing gut bacteria might fight off the introduction of newcomers.

The role of gut microbes

There has been a recent flurry of research about the microbes that inhabit the human body. For instance, a study published earlier this week found that people whose breath contains high concentrations of both hydrogen and methane gases may harbour gut microbes that contribute to weight gain.

"We evolved with these organisms for hundreds of thousands of years and we simply don't know all the things they are doing inside us," said the study's lead author, Dr. Ruchi Mathur, director of the diabetes outpatient clinic at Cedars-Sinai Medical Center in Los Angeles.

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She noted in ancient times such microbes might have helped people store energy when food was scarce. But with today's bountiful supply of food – much of it rich in sugar and fat – some of these microbial inhabitants may be adding fuel to the obesity epidemic.

"It is like our external environment has changed more than our internal environment. It kind of becomes maladaptive even though, a long time ago, it was a good thing," added Mathur, whose study was published in The Journal of Clinical Endocrinology & Metabolism.

So what leads one person to be populated by different types of microbes than another? "We don't know," acknowledged Mathur. But it seems an individual's microbial community is well established by the age of five or six. Many factors may influence the content of that community, including genetics, the type of birth, breastfeeding and early exposure to antibiotics.

"Research into obesity is in its infancy. It is very complex and we keep finding more and more things that might be responsible," she said.

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