Duodenal-jejunal lining increases postprandial unconjugated bile acid responses and disrupts the bile acid-FXR-FGF19 axis in humans

Abstract

Background and aims: Placement of the duodenal-jejunal bypass liner (DJBL) leads to rapid weight loss and restoration of insulin sensitivity in a similar fashion to bariatric surgery. Increased systemic bile acid levels are candidate effectors for these effects through postprandial activation of their receptors TGR5 and FXR. We aimed to quantify postprandial bile acid, GLP-1 and FGF19 responses and assess their temporal relation to the weight loss and metabolic and hormonal changes seen after DJBL placement.

Methods: We performed mixed meal testing in 17 obese patients with type 2 diabetes mellitus (DM2) directly before, one week after and 6 months after DJBL placement.

Results: Both fasting and postprandial bile acid levels were unchanged at 1 week after implantation, and greatly increased 6 months after implantation. The increase consisted of unconjugated bile acid species. 3 hour-postprandial GLP-1 levels increased after 1 week and were sustained, whereas FGF19 levels and postprandial plasma courses were unaffected.

Conclusions: DJBL placement leads to profound increases in unconjugated bile acid levels after 6 months, similar to the effects of bariatric surgery. The temporal dissociation between the changes in bile acids, GLP-1 and FGF19 and other gut hormone responses warrant caution about the beneficial role of bile acids after DJBL placement. This observational uncontrolled study emphasizes the need for future controlled studies.

Keywords: Bile acids; Duodenal-jejunal bypass liner; FGF-19; Obesity; Type 2 diabetes.