The logic behind weight-loss surgery seems simple: rearrange the digestive tract so the stomach can hold less food and the food bypasses part of the small intestine, allowing fewer of a meal's calories to be absorbed. Bye-bye, obesity.
A study of lab mice, published on Wednesday, begs to differ. It concludes that one of the most common and effective forms of bariatric surgery, called Roux-en-Y gastric bypass, melts away pounds not - or not only - by re-routing the digestive tract, as long thought, but by changing the bacteria in the gut.
Or, in non-scientific terms, the surgery somehow replaces fattening microbes with slimming ones.
If that occurs in people, too, then the same bacteria-changing trick achieved by gastric bypass might be accomplished without putting obese patients under the knife in an expensive and risky operation.
"These elegant experiments show that you can mimic the action of surgery with something less invasive," said Dr. Francesco Rubino of Catholic University in Rome and a pioneer in gastric-bypass surgery. "For instance, you might transfer bacteria or even manipulate the diet" to encourage slimming bacteria and squelch fattening kinds, said Rubino, who was not involved in the study.
For many obese patients, particularly those with type 2 diabetes, gastric bypass has succeeded where nothing else has. Severely obese patients routinely lose 65 to 75 percent of their excess weight and fat after the operation, studies show, and leave their diabetes behind.
Oddly, however, the diabetes remission often occurs before significant weight loss. That has made bypass surgeons and weight-loss experts suspect that Roux-en-Y changes not only anatomy but also metabolism or the endocrine system. In other words, the surgery does something besides re-plumb the gut.
That "something," according to previous studies, includes altering the mix of trillions of microbes in the digestive tract. Not only are the "gut microbiota" different in lean people and obese people, but the mix of microbes changes after an obese patient undergoes gastric bypass and becomes more like the microbiota in lean people.
Researchers did not know, however, whether the microbial change was the cause or the effect of post-bypass weight loss.
That is what the new study, by researchers at Massachusetts General Hospital and Harvard University, set out to answer.
They first performed Roux-en-Y on obese mice. As expected, the animals quickly slimmed down, losing 29 percent of their weight and keeping it off, the researchers report in the journal Science Translational Medicine.
To make sure there was not something about the general experience of surgery, rather than gastric bypass specifically, that affected the animals, the scientists performed sham Roux-en-Y on other obese mice. In this procedure, the researchers made incisions as if they were going to do a gastric bypass, but instead connected everything up as nature had it.
The researchers then transferred gut microbiota from the Roux-en-Y mice to microbe-free obese mice. Result: the recipient mice lost weight and fat - no surgery required. Crucially, obese mice that received gut bugs from mice that had received sham Roux-en-Y, not the real thing, did not slim down.
It is the first experimental evidence that changes in the gut microbiota cause the weight loss after gastric bypass, and that the new, post-bypass mix of microbes can cause weight loss in animals that did not have surgery.
In particular, just a week after surgery the Roux-en-Y mice harbored relatively more of the same types of bacteria that become more abundant in people after gastric bypass and that lean people have naturally.
"The effects of gastric bypass are not just anatomical, as we thought," said Dr. Lee Kaplan, senior author of the study and associate professor of medicine at Harvard Medical School. "They're also physiological. Now we need to learn more about how the microbiota exert their effects."
Slimming bacteria work their magic in either of two ways, studies of gut microbiota show. They seem to raise metabolism, allowing people to burn off a 630-calorie chocolate chip muffin more easily.
They also extract fewer calories from the muffin in the first place. In contrast, fattening bacteria wrest every last calorie from food.
Transferring slimming bacteria into obese people might be one way to give them the benefits of weight-loss surgery without an operation. It might also be possible to devise a menu that encourages the proliferation of slimming bacteria and reduces the population of fattening bacteria.
Another new study published this week found people might be able to find out if they have slimming gut germs or fattening one using a breath test.