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Redirecting the flow of bile to the distal small intestine could provide metabolic health benefits similar to bariatric surgery

A new study in mice suggests that diversion of bile acids directly to the distal segment of the small intestine could lead to weight loss and metabolic benefits that are similar to gastric bypass bariatric surgery. For some people with severe obesity who are unable to lose sufficient weight through lifestyle changes alone, bariatric surgery could be an effective therapeutic option. Roux-en-Y gastric bypass (RYGB) surgery, currently the most common bariatric surgery procedure performed in the United States, connects the upper stomach to the middle part of the small intestine (called the jejunum), so that food bypasses a large portion of the gastrointestinal tract in which digestion and nutrient absorption normally take place. RYGB can have dramatic health benefits, including significant weight loss, improved control of blood glucose (sugar) levels, or even reversal of type 2 diabetes. Recent evidence suggests that bile acids help mediate some of the metabolic effects of RYGB. Bile acids, released from the gall bladder into the upper portion of the small intestine (called the duodenum), normally aid in the digestion and absorption of nutrients, and also act as hormones in the gut, influencing metabolism and other physiological processes.

To determine whether bile acids can directly lead to weight loss and metabolic benefit in the absence of RYGB, researchers tested in male mice different surgical procedures connecting the gall bladder to the three portions of the small intestine: the duodenum (GB-D); the jejunum (GB-J); or the ileum (GB-IL), which is farthest from the stomach. The GB-J and GB-IL procedures diverted bile flow, while the GB-D procedure did not alter bile flow and served as a surgical control. They compared mice that underwent these procedures with mice that had RYGB, as well as with mice that did not have any surgical procedures. All mice were fed a high-fat diet to induce obesity. At 2 weeks following surgery, the GB-IL mice and RYGB mice consumed significantly less food than mice in the other groups. After 8 weeks, GB-IL mice exhibited sustained weight loss equal to or even greater than RYGB; GB-D and GB-J mice lost weight initially, but regained weight over time and eventually reached the weight of the normal control mice. Total circulating bile acid levels were elevated several-fold in the GB-IL mice over each other group. The researchers then examined various indicators of metabolic health in the different groups of mice. The GB-IL and RYGB procedures led to several health improvements over the other groups, including sustained weight loss, reduced overall body fat, improved blood glucose control and insulin sensitivity, lower levels of circulating fats, and protection from fat accumulation in the liver. Circulating cholesterol levels were only lower in GB-IL mice. By contrast, triglycerides in the blood were at about the same level among all groups. Because the gut microbiome—the community of bacterial species that symbiotically inhabit the gastrointestinal tract in mice and humans—is known to affect bile acid function, the scientists compared the microbiomes of the groups of mice that received bile diversion procedures. They found that 8 weeks after surgery, the pattern of GB-IL gut bacterial species more closely resembled that of lean mice than of the other surgical groups or control obese mice. These results suggest that surgical diversion of bile to the ileum yields many of the health benefits of RYGB, without the risks associated with dramatic alterations to the gastrointestinal tract. However, the researchers point out that there is still risk associated with surgically diverting bile flow. While promising as a potential treatment for severe obesity, additional research will be necessary to determine if bile diversion surgical procedures could provide similar benefit to humans, or whether these findings could lead to therapeutic approaches that can harness the metabolic potential of bile acids without the need for invasive surgery.

Flynn CR, Albaugh VL, Cai S,…Abumrad NN. Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun 6: 7715, 2015.