Deoxycholic Acid Modulates Cell-Junction Gene Expression and Increases Intestinal Barrier Dysfunction.
Level 5 - mechanism / opinion, no new human data
In vitro cell culture study using Caco-2 monolayers.
PubMed 35163990 · doi:10.3390/molecules27030723
What was done
Human Caco-2 intestinal epithelial cell monolayers were challenged with deoxycholic acid (DCA) at physiological, sub-millimolar concentrations (including 0.25 mM). Investigators evaluated barrier integrity, intracellular reactive oxygen species (ROS) production, ERK1/2 signaling, expression of cell-junction genes via PCR array, and occludin protein content using biochemical and immunofluorescent assays.
What was found
DCA increased transcellular and paracellular permeability by >20% and increased intracellular ROS production by >100%, accompanied by a >40% decrease in ERK1/2 signaling pathways. In cells treated with 0.25 mM DCA, mRNA levels of 23 genes related to tight junction, focal adhesion, gap junction, and adherens junction pathways decreased by >40% compared to untreated controls. Furthermore, DCA decreased occludin protein content at tight junctions and the nucleus by >58%.
Why it matters
This study outlines specific mechanistic pathways showing how elevated secondary bile acids, commonly elevated by high-fat diets, directly disrupt gut epithelial integrity and suppress junctional gene networks.
Limits
The findings derive exclusively from an in vitro human Caco-2 cell culture model and lack in vivo animal or human clinical validation. The model does not capture gut microbiome interactions, mucosal dynamics, or immune system modulation, and sample/replicate sizes are not reported in the abstract.
Cited by
- context Bile acids such as deoxycholic acid released during fat digestion cause endotoxin release.