More than 150,000 Americans undergo weight loss surgery annually. But according to a new study, it may be possible to ditch the scalpel but still reap the benefits of the procedure, either through drugs or even, possibly, changes to the diet.

Thirty-five percent of Americans are now obese, and collectively, the ailments resulting from that obesity – heart disease, stroke, type 2 diabetes and certain types of cancer – are “some of the leading causes of preventable death” and cost the U.S. health care system nearly $150 billion annually, according to estimates from the Centers for Disease Control and Prevention.

But in an environment that contains too much food and too little opportunity for exercise, getting off all those extra pounds, and particularly keeping them off, is notoriously difficult.

In contrast to behavioral strategies, which have high long-term failure rates, weight loss surgery does work. In fact, Randy Seeley of the University of Cincinnati said, it works “much better than anything else we have to give patients today. It’s a fantastic thing, other than two pieces.”

For one thing, the procedure is becoming a victim of its own success in terms of access. “We don’t have enough surgery tables, we don’t have enough surgeons” to perform the surgeries on everyone who could benefit from it.

Even if there were enough supply to meet the demand, surgery is surgery no matter how routine – and weight loss surgery in particular has a relatively high rate of follow-up.

The American Society for Metabolic & Bariatric Surgery does list a change in satiety hormones as an advantage of several types of weight loss surgery. But the going explanation for why gastric surgery works is a mostly mechanical one – there is literally no room for food.

“The logic has been that we’re making a small pouch, and it doesn’t feel good to continue to put calories into that pouch,” Seeley explained.

Seeley and his team, however, suspected that reducing the stomach volume is at best a small part of how bariatric surgeries work.

“It really isn’t about the mechanical aspects of making the stomach smaller, it’s about the signals – how our gut talks to our brain, our pancreas and our liver,” he said. “And what the surgeries are doing is changing that communication.”

In their work, Seeley and his team focused on bile acids, which are made in the liver and secreted into the intestine during eating. Bile acids are best known as digestive acids, but that is not their only role.

“They are not just chemicals that break down fat,” Seeley explained. “They are hormones” that act on distant receptors “in the same way as insulin can.”

In earlier animal studies, Seeley and his team had shown that by manipulating bile acids, they could achieve results that were “very similar to what you get out of [surgery]. . . . They lose weight; they improve on a variety of metabolic parameters.”

They also showed that the bile acids’ most likely was the nuclear receptor FXR, which mediated gene expression changes in response to those acids.

In their current experiments, which they published in the March 27, 2014, issue of Nature, the team did weight loss surgery in FXR knockout mice – and found that their smaller stomachs did the animals no good in terms of weight control.

“The animals that didn’t have FXR failed to lose significant weight, didn’t reduce their food intake, and their glucose levels didn’t improve after the procedure,” Seeley summarized in a podcast that was published along with the paper. “Making a small stomach is not sufficient.”

Seeley and his team looked at the effects of bile acids not just on distant organs, but also on the gut microbiome – which is increasingly being recognized as an organ of sorts in its own right. They found that bile acid signaling changed the composition of the gut flora in ways that are associated with weight loss, though in their paper, the team noted that such changes by themselves are probably not sufficient to induce weight loss by themselves.

The results suggest that in principle, “we should be able to produce the beneficial effects of the surgery without a stapler and a scalpel” by manipulating bile acid signaling, the gut bacteria that respond to bile acids, or both.

And although therapeutics would be one way to do so, Seeley pointed out that they are not the only option. “If the gut bacteria are important, then we can change those through nutritional changes,” he said. “We don’t necessarily have to think about this just in [terms of] drugs.”