Duodenal Mucosal Barrier in Functional Dyspepsia [miRNA]

Epithelial Barrier and Leaky Gut in Dyspepsia Running title: Epithelial Barrier and Leaky Gut in Dyspepsia Context: Some studies suggest that FD is associated with ex vivo duodenal epithelial micro-inflammation and barrier impairment; the pathogenesis of these findings is unclear. miRNAs reduce expression of epithelial barrier genes and have been postulated to increase epithelial permeability in irritable bowel syndrome. New findings: Compared to controls, there is reduced mRNA expression of several barrier proteins (zona occludin-1), increased expression of several miRNAs (eg, miR-142-3p) that suppress the genes for barrier proteins in FD. However, mucosal eosinophils, intraepithelial lymphocytes, and mast cells, ex- and in vivo permeability (urinary lactulose and mannitol excretion) were not significantly different in FD. Impact: Patients with FD do not have a leaky gut syndrome. Overall design: We compared the duodenal mucosal gene expression and miRNAs, in vivo permeability (lactulose-mannitol excretion for 2h after ingestion), ex vivo assessments (transmucosal resistance [TMR], FITC-dextran flux, and basal ion transport), and duodenal histology (light and electron microscopy) in patients with FD and controls.