Gastric bypass leads to the remission of type 2 diabetes independently of weight loss. Our hypothesis
is that changes in bile flow due to the altered anatomy may partly explain the metabolic
outcomes of the operation. We prospectively studied 12 patients undergoing gastric bypass and
six patients undergoing gastric banding over a 6-wk period. Plasma fibroblast growth factor
(FGF)19, stimulated by bile acid absorption in the terminal ileum, and plasma bile acids were
measured. In canine and rodent models, we investigated changes in the gut hormone response
after altered bile flow. FGF19 and total plasma bile acids levels increased after gastric bypass
compared with no change after gastric banding. In the canine model, both food and bile, on their
own, stimulated satiety gut hormone responses. However, when combined, the response was
doubled. In rats, drainage of endogenous bile into the terminal ileum was associated with an
enhanced satiety gut hormone response, reduced food intake, and lower body weight. In conclusion,
after gastric bypass, bile flow is altered, leading to increased plasma bile acids, FGF19, incretin.
and satiety gut hormone concentrations. Elucidating the mechanism of action of gastric bypass
surgery may lead to novel treatments for type 2 diabetes.