Published online Aug 21, 2022. doi: 10.3748/wjg.v28.i31.4328
Peer-review started: March 11, 2022
First decision: May 10, 2022
Revised: May 12, 2022
Accepted: July 25, 2022
Article in press: July 25, 2022
Published online: August 21, 2022
Bile acids have proved to be signaling molecules in mediating metabolic benefits and circulating bile acids were found to be increased following duodenal-jejunal bypass (DJB). However, whether and how the bile acids take effect in the amelioration of metabolic disorders after DJB remain unknown.
Circulating bile acids reflect the amount of bile acids within the gut. It has been proved that luminal bile acids take effect via Takeda G-protein-coupled receptor 5 and nuclear farnesoid X receptor (FXR). However, different subtypes of bile acids have distinct effect on the downstream pathway of FXR and hence, a further investigation of luminal bile acids after DJB is of great significance.
To investigate changes and mechanisms of luminal bile acids in mediating metabolic benefits following DJB.
Salicylhydroxamic acid (SHAM), DJB, and DJB with oral chenodeoxycholic acid (CDCA) supplementation were performed in a high-fat-diet/streptozotocin-induced diabetic rat model. Body weight, energy intake, oral glucose tolerance test, luminal bile acids, serum ceramides and intestinal ceramide synthesis were analyzed at week 12 postoperatively.
Compared to SHAM, DJB achieved rapid and durable improvement in glucose tolerance and led to increased total luminal bile acid concentrations with preferentially increased proportion of FXR - inhibitory bile acids within the common limb. Intestinal ceramide synthesis was repressed with decreased serum ceramides, and this phenomenon could be partially antagonized by luminal supplementation of FXR activating bile acid CDCA.
DJB significantly changes luminal bile acid composition with increased proportion FXR-inhibitory bile acids and reduces serum ceramide levels. There observations suggest a novel mechanism of bile acids in metabolic regulation after DJB.
Mechanisms of bile acids in mediating metabolic benefits after bariatric surgery.