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Extreme weight loss surgery works, but is it thanks to the knife—or the microbes?

If you need to lose a lot of weight, surgeons have a drastic option: They can reroute and sometimes remove parts of your stomach, making it smaller. But instead of limiting the amount of food you can eat, the surgery may work by triggering long-term changes in the types of microbes that inhabit your intestines, a new study suggests. If so, altering the kinds of microbes that live in your gut may be a simpler—and safer—route to weight loss.

The research provides “some of the best evidence in humans so far” that bariatric surgery works “in part by changing the bacteria in your gut,” says David Cummings, an endocrinologist at the University of Washington, Seattle, who was not involved with the work.

Weight loss isn’t the only benefit of so-called bariatric surgery. If a patient has diabetes, for instance, it will usually disappear. The surgery alters metabolism and digestive system functions in several ways, and researchers are still trying to pin down why it’s effective. “This is not about making your stomach small,” says Randy Seeley, an obesity and diabetes researcher at the University of Michigan, Ann Arbor, who wasn’t connected to the study.

One way that bariatric surgery might trigger its effects is through its influence on the microbiota, the swarms of microbes that dwell in our intestines and help us digest food. Studies have found that bariatric surgery dramatically alters the microbiota’s makeup in mice and humans. Two years ago, scientists put mice through a Roux-en-Y gastric bypass—a type of bariatric surgery that involves reducing the stomach to a small pouch and stitching it to the middle part of the small intestine—and then transplanted microbes from the slimmed down animals into mice that lacked intestinal bacteria. The recipient rodents lost 5% of their body weight in 2 weeks. But these studies only checked for short-term changes.

Now, researchers are looking for longer term results. Microbiologist Fredrik Bäckhed of the University of Gothenburg in Sweden and colleagues tracked down 14 women who had undergone Roux-en-Y gastric bypass or vertical banded gastroplasty (another type of bariatric surgery that involves stapling off part of the stomach) more than 9 years ago. Although all of the women had lost a substantial amount of weight after their operations, they were still obese, with an average body mass index (BMI) of almost 32. (The cutoff for normal BMI is 25.) The researchers sequenced microbial DNA from the patients’ feces and profiled the types of microorganisms that inhabited their intestines. The team then performed the same procedure on stool samples from seven severely obese women who hadn’t gone through the surgery and served as controls.

The women who’d had Roux-en-Y gastric bypass differed from control patients in the variety and abundance of their microbes, the researchers report online today in Cell Metabolism. However, Bäckhed and colleagues found that women in the two bariatric surgery groups harbored about the same assortment of microbial inhabitants. The two bariatric procedures “cause significant changes in the microbiota, and these changes are long-lasting,” Bäckhed says.

Surgery reduced the abundance of some microbes and boosted the abundance of others, such as the group that includes the best-known intestinal bacterium, Escherichia coli. To determine the effects of these alterations, the researchers transplanted bacteria from the bariatric surgery patients and the control group into germ-free mice. Because these mice carry no intestinal bacteria to help them break down food, they tend to be lean. But they put on fat when they get an infusion of human intestinal bacteria. The rodents that received microbes from the Roux-en-Y gastric bypass patients, however, amassed 43% less fat than did rodents that received microbes from the control patients. Similarly, mice whose microbes came from the vertical banded gastroplasty patients added 26% less fat than did rodents that got microbes from the controls.

Bäckhed and colleagues also showed that the source of a mouse’s microbes affected how it digested food. Mice that received microorganisms from Roux-en-Y gastric bypass group burned fewer carbohydrates and more fat than did rodents whose microbes came from the control patients, possibly explaining the differences in fat accumulation.

The study shows that after bariatric surgery “the microbiome changes are stable,” Seeley says. “It makes sense, but nobody had proved it.”

Researchers hope that tweaking patients’ microbes might provide the benefits of bariatric surgery without the risk of undergoing the procedure. However, scientists still need to nail down which of the roughly 1000 kinds of microbes that inhabit our intestines deliver those benefits, Bäckhed says.