Duodenal Mucosal Barrier in Functional Dyspepsia.
Duodenal Epithelial Permeability
Inflammation
Intestinal Barrier
Tight Junction Gene Expression
Journal
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association
ISSN: 1542-7714
Titre abrégé: Clin Gastroenterol Hepatol
Pays: United States
ID NLM: 101160775
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
21
05
2021
revised:
25
08
2021
accepted:
22
09
2021
pubmed:
5
10
2021
medline:
20
4
2022
entrez:
4
10
2021
Statut:
ppublish
Résumé
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.
Sections du résumé
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.
Identifiants
pubmed: 34607017
pii: S1542-3565(21)01043-0
doi: 10.1016/j.cgh.2021.09.029
pmc: PMC8975906
mid: NIHMS1745363
pii:
doi:
Substances chimiques
MicroRNAs
0
Mannitol
3OWL53L36A
Lactulose
4618-18-2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1019-1028.e3Subventions
Organisme : NIDDK NIH HHS
ID : P01 DK068055
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK084567
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 AGA Institute. Published by Elsevier Inc. All rights reserved.
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