The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control

Abstract

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.

Figures

Fig. 1.

A, Schematic illustration of the anatomy and canulation of the canine model. A gastrostomy tube was placed into the duodenum close to the ampulla of Vater. The common bile duct was ligated and the gallbladder canulated to allow drainage of bile. B, Schematic illustration of the functional anatomy of the bile in ileum group. Transections 1 cm proximal and distal to the drainage point of the common bile duct were performed. The proximal and distal ends of the transected duodenum were anastomosed end to end and continuity restored. The segment of the duodenum containing the common bile duct was anastomosed side to side to the distal jejunum, 10 cm proximally to the terminal ileum.

Fig. 2.

Fasting plasma FGF19 concentrations (median and interquartile ranges) at d 0, 4, and 42 in six gastric banding patients (white bars) and 12 gastric bypass patients (black bars). *, P < 0.05 Mann-Whitney U test. Preop, Preoperatively.

Fig. 3.

Fasting total plasma bile acid concentrations at d 0, 4, and 42 in six gastric banding patients (white bars) and 12 gastric bypass patients (black bars). *, P < 0.05 Mann-Whitney U test. Preop, Preoperatively.

Fig. 4.

A, AUC for the postprandial GLP-1. B, AUC for postprandial PYY response after 400 g of food in dogs pre- or postoperatively either receiving food alone without bile (food), bile alone without food (bile), or food and bile in combination (food + bile).*, P < 0.05. The time course of the postprandial response for GLP-1 (C) and PYY (D).

Fig. 5.

Plasma GLP-1 (A) and PYY (B) levels in rats that had bile draining into their duodenum or bile draining into their ileum.

Fig. 6.

A, Weight of rats in bile-in-duodenum (solid line) and bile-in-ileum (broken line) groups before and up to 28 d after surgery. B, Food intake of bile-in-duodenum (solid line) and bile-in-ileum (broken line) rats before and up to 28 d after surgery. *, P < 0.05.