Dihydroxy bile acids increase mucosal permeability and bacterial uptake in human colon biopsies

Abstract

Objective. Bile acids in mM concentrations are known to increase chloride secretion and alter mucosal permeability in animal colon. Increased mucosal permeability is believed to play an important role in the development of intestinal inflammation. The aim of this study was to investigate the influence of µM concentrations of dihydroxy bile acids on permeability and bacterial uptake in the normal human colon. Material and methods. Endoscopic biopsies from the sigmoid colon of 18 subjects with normal colonic histology were mounted in modified Ussing chambers. Chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) were added to the mucosal compartment. Short-circuit current (Isc) and transepithelial resistance (TER) were studied for 120 min. Cr-EDTA and horseradish peroxidase (HRP) were used to assess paracellular and transcellular permeability, respectively. The transmucosal passage of chemically killed Escherichia coli was quantified and investigated using confocal microscopy. Results. A significant decrease in TER was seen after 60 min of exposure to 1000 µmol/l CDCA and DCA. The combination of E. coli and 100 µmol/l CDCA gave a decrease in TER compared to controls (p=0.06). DCA showed a dose-related increase in Cr-EDTA permeability, which was most pronounced at 1000 µmol/l (p=0.02). Increased E. coli uptake was induced by 500 µmol/l (p=0.01) and 1000 µmol/l CDCA (p=0.04). Bacterial uptake was increased at 100 µmol/l by exposure to DCA (p=0.03). Confocal microscopy revealed the presence of E. coli bacteria in the lamina propria after 15 min of exposure to 1000 µmol/l CDCA and DCA. Conclusions. Our study suggests that dihydroxy bile acids in µM concentrations alter barrier function in normal human colon biopsies, causing increased antigen and bacterial uptake; thereby bile acids may contribute to the development of intestinal inflammation.

• Chenodeoxycholic acid
• deoxycholic acid
• diffusion chamber
• intestinal mucosa
• permeability