(P20-043-25) Prolonged Exposure to Deoxycholic Acid Impairs Intestinal Barrier Function in Caco-2 Cell Model

Objectives: High-fat diets are associated with continuous exposure to bile acids, including deoxycholic acid (DCA), which is known to influence intestinal barrier integrity. While short-term studies have demonstrated transient effects of DCA on epithelial permeability, the impact of prolonged exposure remains underexplored. This study aimed to address this gap by investigating the effects of longer exposure to DCA on intestinal barrier function using a Caco-2 cell model. To evaluate the impact of prolonged exposure to physiological concentrations of DCA on the integrity of the intestinal epithelial barrier using human-derived Caco-2 cell monolayers.

Methods: Caco-2 cells were grown as polarized monolayers on transwell inserts to mimic the intestinal epithelial barrier. Cells were treated for 48 hours with sub-millimolar concentrations (0.1-0.5 mM) of DCA. Barrier integrity was assessed by transepithelial electrical resistance (TEER)measurements and inulin permeability assays. TEER changes were expressed as a percentage decrease relative to untreated controls, and inulin flux was measured to evaluate paracellular permeability.

Results: DCA treatment significantly increased inulin permeability, with > 20% increase observed at 0.5 mM and > 15% at 0.4 mM compared to controls. DCA exposure led to a concentration-dependent decrease in TEER, with > 20% reduction at 0.5 mM, > 15% reduction at 0.4 and 0.3 mM, and > 10% reduction at 0.2 mM. These TEER changes correlated strongly with the observed increases in inulin permeability, indicating a compromised barrier function.

Conclusions: This study highlights that prolonged exposure to physiological concentrations of DCA disrupts intestinal barrier integrity in a concentration-dependent manner. These findings provide novel insights into the potential chronic effects of bile acids in the context of high-fat diets, where sustained DCA exposure could exacerbate intestinal permeability and contribute to the development of metabolic and inflammatory disorders.

Funding Sources: This work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062-10700-002-000D.