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. 2022 May;20(5):1019-1028.e3.
doi: 10.1016/j.cgh.2021.09.029. Epub 2021 Oct 2.

Duodenal Mucosal Barrier in Functional Dyspepsia

Susrutha Puthanmadhom Narayanan  1 , Daniel R O'Brien  2 , Mayank Sharma  1 , Thomas C Smyrk  3 , Rondell P Graham  3 , Madhusudan Grover  1 , Adil E Bharucha  4
Affiliations

Duodenal Mucosal Barrier in Functional Dyspepsia

Susrutha Puthanmadhom Narayanan et al. Clin Gastroenterol Hepatol. 2022 May.

Abstract

Background & aims: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Duodenal Epithelial Permeability; Inflammation; Intestinal Barrier; Tight Junction Gene Expression.

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Conflict of interest statement

Conflict of interest: None

Figures

Figure 1.
Figure 1.
In Vivo Permeability. Lactulose and mannitol excretion between 0-60 minutes (upper panel) and 60-120 minutes (lower panel) in controls and functional dyspepsia (FD).
Figure 2.
Figure 2.
Ex-vivo assessments. Comparison of transmucosal resistance (TMR) (A), basal Isc (B), and rate of FITC–dextran flux measured over 3 hours (C) between controls and FD. Correlation between baseline duodenal transmucosal resistance (TMR) and FITC-dextran flux (D).
Figure 3.
Figure 3.
Reduced Duodenal Mucosal Expression of Barrier Proteins in Functional Dyspepsia. (Used with permission, Mayo Foundation for Medical Education and Research.) All differentially expressed proteins are significant at a false discovery rate less than 0.05.
Figure 4.
Figure 4.
Heat maps showing differentially expressed miRNAs (upper panel) and mRNAs (lower panel) between controls and FD.
See this image and copyright information in PMC

Comment in

References

    1. Vanheel H, Carbone F, Valvekens L, et al. Pathophysiological Abnormalities in Functional Dyspepsia Subgroups According to the Rome III Criteria. American Journal of Gastroenterology 2017;112:132–140. - PubMed
    1. Talley NJ, Walker MM, Aro P, et al. Non-ulcer dyspepsia and duodenal eosinophilia: an adult endoscopic population-based case-control study. Clin Gastroenterol Hepatol 2007;5:1175–83. - PubMed
    1. Vanheel H, Vicario M, Vanuytsel T, et al. Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 2014;63:262–71. - PubMed
    1. Bharucha AE, Camilleri M, Burton DD, et al. Increased nutrient sensitivity and plasma concentrations of enteral hormones during duodenal nutrient infusion in functional dyspepsia. American Journal of Gastroenterology 2014;109:1910–20. - PMC - PubMed
    1. Du L, Chen B, Kim JJ, et al. Micro-inflammation in functional dyspepsia: A systematic review and meta-analysis. Neurogastroenterology & Motility 2018;30:e13304. - PubMed

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