Duodenal Mucosal Barrier in Functional Dyspepsia.

Susrutha Puthanmadhom Narayanan, Daniel R O'Brien, Mayank Sharma, Thomas C Smyrk, Rondell P Graham, Madhusudan Grover, Adil E Bharucha

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 2022 May

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In addition to gastric sensorimotor dysfunctions, functional dyspepsia (FD) is also variably associated with duodenal micro-inflammation and epithelial barrier dysfunction, the pathogenesis and clinical significance of which are unknown. Our hypothesis was that miRNAs and/or inflammation degrade epithelial barrier proteins, resulting in increased duodenal mucosal permeability in FD. We compared the duodenal mucosal gene expression and miRNAs, in vivo permeability (lactulose-mannitol excretion between 0 and 60 and 60 and 120 minutes after saccharide ingestion), ex vivo assessments (transmucosal resistance, fluorescein isothiocyanate [FITC]-dextran flux, and basal ion transport), and duodenal histology (light and electron microscopy) in 40 patients with FD and 24 controls. Compared with controls, the mRNA expression of several barrier proteins (zonula occludens-1, occludin, claudin-12, and E-cadherin) was modestly reduced (ie, a fold change of 0.8-0.85) in FD with increased expression of several miRNAs (eg, miR-142-3p and miR-144-3-p), which suppress these genes. The urinary lactulose excretion and the lactulose:mannitol ratio between 60 and 120 minutes were greater in FD than in controls (P < .05). The FITC-dextran flux, which reflects paracellular permeability, was inversely correlated (r = -0.32, P = .03) with transmucosal resistance and directly correlated (r = 0.4, P = .02) with lactulose:mannitol ratio. Other parameters (mucosal eosinophils, intraepithelial lymphocytes, and mast cells, transmucosal resistance, FITC-dextran flux, average intercellular distance, and proportion of dilated junctions) were not significantly different between groups. In FD, there is a modest reduction in the expression of several duodenal epithelial barrier proteins, which may be secondary to up-regulation of regulatory miRNAs, and increased small intestinal permeability measured in vivo. Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.

Citation

Susrutha Puthanmadhom Narayanan, Daniel R O'Brien, Mayank Sharma, Thomas C Smyrk, Rondell P Graham, Madhusudan Grover, Adil E Bharucha. Duodenal Mucosal Barrier in Functional Dyspepsia. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 May;20(5):1019-1028.e3