Ethanol impairs intestinal barrier function in humans through mitogen activated protein kinase signaling: a combined in vivo and in vitro approach.
Level 2 - randomized trial
Randomized crossover trial in healthy human volunteers
PubMed 25226407 · doi:10.1371/journal.pone.0107421
What was done
Twelve healthy volunteers completed a randomized crossover trial receiving either placebo or 20 g ethanol via intraduodenal administration. Small and large intestinal permeability were assessed. Duodenal mucosal biopsies were analyzed for tight junction protein localization, gene expression, and phosphorylation of mitogen-activated protein kinase (MAPK) isoforms (p38, ERK, and JNK). The signaling pathway was further characterized in vitro using Caco-2 cell monolayers treated with ethanol, MAPK inhibitors, and the antioxidant L-cysteine.
What was found
The abstract reports directions of effect without numerical values or confidence intervals. Intraduodenal ethanol increased small and large intestinal permeability in humans. Duodenal biopsies demonstrated redistribution of ZO-1 and occludin, down-regulation of ZO-1 mRNA, up-regulation of myosin light chain kinase (MLCK) mRNA, and increased phosphorylation of p38, ERK, and JNK. In Caco-2 cell monolayers, ethanol induced permeability, junctional protein and F-actin redistribution, and MAPK/MLCK phosphorylation; these effects were reversed by MAPK inhibitors or L-cysteine.
Why it matters
This study provides direct human trial evidence that even a single moderate dose of ethanol acutely impairs gut barrier integrity across both the small intestine and colon, identifying MAPK activation and MLCK crosstalk as key mechanistic drivers.
Limits
The human trial had a small sample size of 12 healthy participants. Ethanol was administered directly into the duodenum rather than consumed orally, bypassing gastric metabolism. The abstract does not report exact numerical data, variance, or p-values, and findings from an acute single dose in healthy individuals cannot be directly generalized to chronic alcohol intake or clinical populations with existing gastrointestinal disease.
Cited by
- supports Administering a dose of 20 grams of alcohol in humans is sufficient to disrupt the tight junction proteins zonula occludens-1 and occludin.