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Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction.

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Deoxycholic acid (DCA), a bile acid linked to obesity, increases intestinal permeability by disrupting cell junction gene expression and occludin protein levels. This finding highlights DCA

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Area of Science:

  • Gastroenterology
  • Cell Biology
  • Molecular Biology

Background:

  • Diet-related obesity is linked to increased intestinal hyperpermeability.
  • High dietary fat intake elevates colonic bile acids (BAs), notably deoxycholic acid (DCA).

Purpose of the Study:

  • To investigate how DCA affects intestinal barrier integrity and gene expression.
  • To test the hypothesis that DCA modulates cell junction pathways and increases intestinal permeability.

Main Methods:

  • Utilized a human Caco-2 cell intestinal model.
  • Employed cell proliferation, PCR array, biochemical, and immunofluorescent assays.
  • Challenged cells with physiological concentrations of DCA.

Main Results:

  • DCA significantly increased intestinal permeability (transcellular and paracellular).
  • DCA elevated intracellular reactive oxidative species and decreased ERK1/2 signaling.
  • DCA reduced mRNA levels of 23 genes in epithelial barrier pathways and decreased occludin protein.

Conclusions:

  • DCA disrupts the intestinal barrier by decreasing gene expression in cell junction pathways.
  • DCA diminishes occludin protein at tight junctions, contributing to increased intestinal permeability.
  • Findings suggest DCA plays a role in diet-related obesity-induced gut barrier dysfunction.