Vitamin D receptor is overexpressed in the duodenum of patients with irritable bowel syndrome.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, and bile acids are thought to be associated with the pathogenesis of IBS. Bile acid receptors are expressed on intestinal epithelial cells. However, no study has assessed bile acid receptor proteins in IBS. Therefore, we examined the intestinal mucosal expression of bile acid receptors in patients with IBS. METHODS: Intestinal biopsies were performed in patients with IBS and controls. Mast cells, vitamin D receptor (VDR), and somatostatin were stained with specific antibodies. Levels of VDR, farnesoid X receptor (FXR), takeda-G-protein-receptor-5 (TGR5), claudins, and transient-receptor-potential-cation-channel-subfamily-V-member 6 (TRPV6) were assessed by western blotting. RESULTS: 3Mast cell counts in the second part of the duodenum were significantly higher in patients with IBS than in controls. VDR protein levels were significantly elevated in the duodenum and terminal ileum of patients with IBS compared with controls, although this difference was not seen in the cecum or rectum. FXR and TGR5 protein levels did not differ in any part of the intestine. VDR-positive cryptal epithelia in IBS were distributed not only at basal crypt but also along the upper part of the basal crypt epithelial cells. In contrast, the pattern of gut somatostatin-positive cells, claudins, and TRPV6 levels did not differ. CONCLUSIONS: The number of mast cells in the duodenum was significantly increased, and the protein expression levels of VDR, but not those of FXR or TGR5, were elevated in the duodenal epithelial crypt in patients with IBS.

Chenodeoxycholic Acid Releases Proinflammatory Cytokines from Small Intestinal Epithelial Cells Through the Farnesoid X Receptor.

BACKGROUND/AIMS: Bile acids have recently been associated with the pathogenesis of irritable bowel syndrome (IBS). We therefore evaluated the expression of bile acid receptors in the intestinal mucosa of IBS patients as well as the effects of bile acids on small intestinal epithelial cells. METHODS: Intestinal biopsy specimens were obtained from 15 IBS patients and 15 healthy controls. The effects of bile acid stimulation on trans-epithelial electrical resistance (TEER) and permeability in differentiated Caco-2 cells were measured. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay. mRNA levels of bile acid receptors, including farnesoid X receptor (FXR), and cytokines were determined by real-time reverse transcription-PCR. Caco-2 cells were pre-incubated with the FXR antagonist guggulsterone. RESULTS: FXR mRNA expression at the terminal ileum was increased in IBS patients. Chenodeoxycholic acid (CDCA) significantly decreased TEER, increased permeability, and increased interleukin-8 (IL-8) release from Caco-2 cells. Pre-incubation with guggulsterone blocked CDCA-mediated IL-8 release; however, the decrease in TEER was not reversed. CDCA-induced IL-6 and IL-8 mRNA levels were blocked by guggulsterone. CDCA increased IL-6, tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor release, whereas guggulsterone significantly blocked IL-6 and TNF-α release. CONCLUSIONS: FXR expression was elevated at the terminal ileum in IBS patients. CDCA increased proinflammatory cytokines, while guggulsterone blocked these increases.

Systematic review with meta-analysis: Vonoprazan, a potent acid blocker, is superior to proton-pump inhibitors for eradication of clarithromycin-resistant strains of Helicobacter pylori.

BACKGROUND: Vonoprazan is a novel gastric acid suppressant that is applied in Japan to treat gastric diseases including Helicobacter pylori (H. pylori) infection. This meta-analysis aimed to summarize the ability of vonoprazan to eradicate clarithromycin-susceptible and clarithromycin-resistant H. pylori strains. MATERIALS AND METHODS: A systematic search was performed using PubMed, EMBASE, Web of Science, and Cochrane Library. Studies were included if they evaluated eradication rates of vonoprazan-based and conventional PPI-based triple therapies and checked for clarithromycin susceptibility of H. pylori. RESULTS: We identified 5 studies including a total of 1599 patients containing data regarding H. pylori with clarithromycin susceptibility. Among those infected with clarithromycin-susceptible H. pylori, eradication rates for vonoprazan-based and conventional PPI-based therapies did not significantly differ in either the randomized (RCT; pooled eradication rates, 95.4% vs 92.8%; pooled odds ratio [OR], 1.63; 95% confidence intervals [CI], 0.74-3.61; P = .225) and nonrandomized (NRCT; pooled eradication rates, 92.9% vs 86.2%; OR, 4.58; 95% CI, 0.67-31.45; P = .122) controlled trials. However, vonoprazan-based triple therapy was significantly superiority to PPI-based therapy for patients with clarithromycin-resistant strains in both RCT (pooled eradication rates, 82.0% vs 40.0%; OR, 6.83; 95% CI, 3.63-12.86; P < .0001) and NRCT (pooled eradication rates, 80.8% vs 41.8%; OR, 4.98; 95% CI, 2.47-10.03; P < .0001). CONCLUSIONS: Vonoprazan-based and conventional PPI-based therapies are similarly effective for the eradication of clarithromycin-susceptible H. pylori strains. Vonoprazan is superior to conventional PPI-based therapy for the eradication of clarithromycin-resistant H. pylori strains. However, clarithromycin was misused because the combination of vonoprazan and amoxicillin cures approximately 80% of infections without clarithromycin.