Expression of bile acid receptors and transporters along the intestine of patients with type 2 diabetes and controls.

Abstract

The enterohepatic circulation of bile acids depends on intestinal absorption by bile acid transporters and activation of bile acid receptors, which stimulates secretion of hormones regulating glucose and lipid metabolism and appetite. Distribution of bile acid transporters and receptors in the human gut and their potential involvement in type 2 diabetes (T2D) pathophysiology remain unknown. We explored the expression of genes involved in bile acid metabolism throughout the intestines of patients with T2D and matched healthy controls. Intestinal mucosa biopsies sampled along the intestinal tract in 12 individuals with T2D and 12 healthy controls were subjected to mRNA sequencing. We report expression profiles of apical sodium-dependent bile acid transporter (ASBT), organic solute transporter (OST) α/β, farnesoid X receptor (FXR), Takeda G receptor 5 (TGR5), fibroblast growth factor 19 (FGF19) and FGF receptor 4 (FGFR4). Expression of ASBT and OSTα/β was evident in the duodenum of both groups with increasing levels through the small intestine, and no (ASBT) or decreasing levels (OSTα/β) through the large intestine. The FXR expression pattern followed that of OSTα/β whereas FGFR4 were evenly expressed through the intestines. Negligible levels of TGR5 and FGF19 were evident. Patients with T2D exhibited lower levels of FGF19, FXR, ASBT and OSTα/β mRNAs compared with healthy controls, although the differences were not statistically significant after adjusting for multiple testing. We demonstrate distinct expression patterns of bile acid transporters and receptors through the intestinal tract with signs of reduced ASBT, OSTα/β, FXR and FGF19 mRNAs in T2D.