Duodenal Mucosal Barrier in Functional Dyspepsia

Area of Science:

• Gastroenterology
• Molecular Biology
• Physiology

Background:

• Functional dyspepsia (FD) involves gastric issues and potential duodenal micro-inflammation.
• Epithelial barrier dysfunction in the duodenum is observed in FD, but its cause and significance are unclear.
• This study investigates the role of microRNAs (miRNAs) and inflammation in degrading duodenal epithelial barrier proteins.

Purpose of the Study:

• To determine if miRNAs and/or inflammation degrade duodenal epithelial barrier proteins in FD.
• To assess if this degradation leads to increased duodenal mucosal permeability in FD patients.

Main Methods:

• Compared duodenal gene expression, miRNA profiles, and in vivo permeability (lactulose-mannitol test) in 40 FD patients and 24 controls.
• Performed ex vivo assessments of transmucosal resistance and fluorescein isothiocyanate (FITC)-dextran flux.
• Analyzed duodenal histology using light and electron microscopy.

Main Results:

• FD patients showed reduced mRNA expression of barrier proteins (zonula occludens-1, occludin, claudin-12, E-cadherin) compared to controls.
• Increased expression of specific miRNAs (miR-142-3p, miR-144-3p) that target these barrier protein genes was observed in FD.
• FD patients exhibited increased in vivo small intestinal permeability, indicated by higher urinary lactulose excretion and lactulose:mannitol ratio.

Conclusions:

• Functional dyspepsia is associated with a modest reduction in duodenal epithelial barrier proteins.
• Up-regulation of specific miRNAs may contribute to the reduced expression of these barrier proteins in FD.
• Increased small intestinal permeability is a feature of functional dyspepsia.