Bile acids induce intracellular acidosis and ATP depletion in human colonic crypts

Introduction: Under pathophysiological conditions, bile acids can reach the large intestine in high concentrations and can induce watery diarrhoea. This could be due to reduced Cl- or Na+ uptake or stimulated fluid and Cl- secretion. Aims: Our aim was to investigate the effects of bile acids on human colonic epithelial cells.

Methods: Colonic biopsies were obtained from patients with negative colonoscopic finding. After collagenase digestion, the isolated colonic crypts were loaded with the pH sensitive fluorescent dye BCECF. The intracellular ATP level (ATPi) was determined using Mg-green dye which has been shown that indirectly reflect the changes in ATPi. Intracellular pH (pHi) and ATPi were measured by a microspectrofluorimeter system. The crypts were continuously perfused with Na+-containing Hepes-buffered solution.

Results: We examined the effects of bile acids on the proximal and distal part of the colon and on the base, surface and middle parts of the isolated colonic crypts. We observed that both chenodeoxycholic acid (CDC) and glycochenodeoxycholic acid (GCDC) caused dose-dependent acidosis in the colonic crypts. The pHi change in case of the non-conjugated CDC was significantly greater compared to the conjugated GCDC. In addition, administration of CDC in high concentration (1 mM) significantly reduced ATPi. There were no significant differences in the pHi and ATPi alterations between the proximal and distal colon and between the three parts of the isolated colonic crypts.

Conclusion: Bile acids cause intracellular acidosis and ATPi depletion in the colonic epithelial cells, which may reduce the fluid and electrolyte absorption in the colon.

This work was supported by OTKA, MTA and NKTH.