July 21, 2015

Study finds rerouting bile acids may offer simpler alternative to gastric bypass surgery

A new surgical procedure could offer a simpler approach to achieve some of the same weight-loss and metabolic benefits associated with gastric bypass surgery, researchers at VUMC report.

A new surgical procedure could offer a simpler approach to achieve some of the same weight loss and metabolic benefits associated with gastric bypass surgery, researchers at VUMC report.

In a study published recently in Nature Communications, the researchers describe a procedure that involves rerouting the flow of bile acids to be introduced much later in the digestive process.

The researchers found that by surgically diverting bile acids from the liver and gallbladder in mice to an area farther down the small intestine, many of the same benefits of gastric bypass surgery were observed, such as reducing obesity, improving diabetes and reversing fatty liver disease.

“It is a pretty surprising finding,” said Naji Abumrad, M.D., professor of Surgery and the John L. Sawyers Professor of Surgical Sciences, who led the study. “If the same happens in humans, this should ultimately represent a much easier approach.”

Bile acids are produced by the liver and help the body digest fat in the small intestine. But in recent years, scientists have identified that bile acids do more than that, playing roles in energy metabolism, blood sugar regulation and even affecting the makeup of intestinal bacteria.

The researchers tested rerouting bile to several locations along the small intestine in the mice and found that the greatest benefit came from diverting bile flow to the ileum, which is the final section of the small intestine before waste reaches the large intestine.

“The benefit was progressive,” Abumrad said. “As you go further down the small intestine, you get a higher benefit. So the issue is, where is the sweet spot?”

The results of the new procedure were compared to the benefits of Roux-en-Y gastric bypass surgery, a highly effective procedure that involves creating a small stomach pouch to restrict food intake and then joining that pouch directly to the small intestine, bypassing most of the stomach and part of the small intestine.

Mice that had undergone the procedure to divert bile to the final section of the small intestine ate less and had similar weight loss as the group with the gastric bypass surgery — and in some cases had even greater weight loss and improvement of diabetes.

The researchers suggested that the causes of the weight loss with the new procedure could be related to less fat absorption and increased energy expenditure, among other causes.

Aside from the potential to adapt the procedure for clinical use, the findings could also potentially lead to medication designed to produce the same metabolic benefits of the bile diversion without the surgery, the researchers said.

“The ultimate goal is to put the effects of this procedure in a pill,” said Robb Flynn, Ph.D., assistant professor of Surgery.

One of the next steps for the researchers is to study whether bile acids activate a specific “pathway” that leads to the metabolic improvements, something that could be targeted through medicine. The group has received a $1.25 million grant from the National Institutes of Health to study during the next five years the physiology behind the procedure.

“If we could figure out the identity of this pathway, it could also help patients who don’t respond very well to bariatric surgery or help the people who are unable to undergo the operation get down to a safer body weight so that they could have the procedure,” said Vance Albaugh, M.D., Ph.D., a postdoctoral fellow and General Surgery resident who worked on the study.