Duodenal mucosal secretory disturbances in functional dyspepsia

Background There is increased recognition of duodenal disturbances (inflammation, altered mucosal protein expression, and chemosensitivity) in functional dyspepsia (FD). Besides sensorimotor functions, enteric submucosal neurons also regulate epithelial ion transport. We hypothesized that duodenal mucosal ion transport and expression of associated genes are altered in FD. Methods Duodenal mucosal ion transport (basal and acetylcholine- and glucose-evoked changes in short-circuit current [Isc]) and expression of associated genes and regulatory miRNAs were evaluated in 40 FD patients and 24 healthy controls. Results Basal Isc (FD: 88.2 [52.6] mu A/cm(2)vs healthy: 20.3 [50.2] mu A/cm(2);P <= .0001), acetylcholine-evoked Isc (FD: Emax 50.4 [35.8] mu A/cm(2)vs healthy: 16.6 [15] mu A/cm(2);P <= .001), and glucose-evoked Isc responses (FD: E(max)69.8 [42.1] mu A/cm(2)vs healthy: 40.3 [24.6] mu A/cm(2);P = .02) were greater in FD than in controls. The Emax for glucose was greater in FD patients on selective serotonin reuptake inhibitors. In FD, the mRNA expression ofSLC4A7andSLC4A4, which transport bicarbonate into cells at the basolateral surface, and the apical anion exchangerSLC26A3were reduced (false discovery rate <0.05), the serotonin receptorHTR4was increased, and the serotonin transporterSLC6A4was decreased. Selected miRNAs (hsa-miR-590-3p, hsa-miR-32-5p) that target genes associated with ionic transport were upregulated in FD. Conclusions Compared to controls, FD patients had greater baseline and agonist-evoked duodenal mucosal secretory responses. These findings may be explained by reduced gene expression, which would be anticipated to reduce luminal bicarbonate secretion. The upregulated miRNAs may partly explain the downregulation of these genes in FD.

Automated summary

It is increasingly recognized that duodenal disturbances play a role in functional dyspepsia (FD), affecting mucosal ion transport and gene expression. In this study, duodenal mucosal ion transport and associated gene expression were found to be altered in FD patients compared to healthy controls. The findings suggest that upregulated miRNAs may contribute to the downregulation of genes involved in ion transport in FD.