Stomach-shrinking gastric bypass surgery is a powerful, though risky, way to combat extreme obesity. Now, scientists have discovered a way to achieve some of the procedure’s potent effects without the surgery, raising the possibility that new and less invasive obesity therapies could be developed.
Scientists have long been intrigued by a peculiar fact about gastric bypass surgery: It is effective — far more effective than it logically should be, if it is really just limiting absorption of nutrients. Beyond just weight loss, the operation increases energy expenditure, boosts the hormones released by the gut, and improves the body’s ability to regulate blood sugar — so much in some patients that their type 2 diabetes disappears. Researchers wanted to know why.
In a study published Wednesday in the journal Science Translational Medicine, researchers from Massachusetts General Hospital and Harvard University showed that if they transplant the gut microbes from a mouse that has received gastric bypass surgery into a mouse whose gut is a blank slate, that mouse will lose weight. This suggests that the surgery’s success might depend in part on changing the mix of bacteria in the gut.
Many questions remain about whether such a procedure could work in people — and if it did, how often it would have to be repeated, since the researchers expect that the gut flora will begin to revert back toward its normal state. But it’s a promising step toward understanding how gastric bypass works and possibly developing an intervention that could mimic it.
“The more we understand about how the bypass works, the more we could potentially increase it without doing the surgery,’’ said Dr. Lee Kaplan, director of the Obesity, Metabolism & Nutrition Institute and Gastrointestinal Unit at Mass. General, who led the work with Peter Turnbaugh at Harvard.
Kaplan said that he hopes to move toward a clinical trial over the coming year, but that more research is needed. Researchers are testing, for example, whether the gut microbe transplant will take hold in a mouse that already has its own population of microbes, instead of the particular laboratory strain used in the current experiment. Researchers are also doing animal experiments to understand whether laxatives or antibiotics might be useful in clearing out the existing gut microbe community to help the new one become established.
Ultimately, interventions could span a wide gamut. One possibility is a fecal transplant, in which donor feces are transplanted using a colonoscopy — a procedure already used to treat C. difficile infections. But Kaplan also hopes to explore more deeply the precise changes the bypass surgery induces in the population of gut bacteria. That knowledge could guide experiments that could test whether simply administering the right ratio of bacteria might be a way to induce weight loss.
One day, he said, an obesity therapy could potentially be administered in the form of a specially-designed yogurt.