Chloride Channel ClC-2 is a Key Factor in the Development of DSS-induced Murine Colitis:

Previously, we have shown that the chloride channel ClC-2 modulates intestinal tight junction (TJ) barrier function. The aim of the present study was to investigate the role of ClC-2 in epithelial barrier function and recovery in the event of epithelial injury

Understanding the health risks and emerging concerns associated with the use of long-term proton pump inhibitors

Abstract Background Proton pump inhibitors (PPIs) are the most efficacious and common medications for gastric acid suppression. However, PPIs continue to perpetuate safety concerns due to the availability as an over-the-counter medication. This uncontrolled use of PPIs has recently been shown to be associated with the increased health risks. Main body of the abstract The inhibition of gastric acid production by irreversibly binding to and inhibiting the H+/K+ ATPase enzyme system can cause structural and physiologic changes in the GI microbiome, GI physiology, and pH. With the recent guideline updates from American Gastroenterological Association regarding deprescription of PPIs, this review focuses on the complications of long-term use of PPIs on various systems, gut microbiome, intestinal barrier and inflammatory bowel disease (IBD). Short conclusion If PPI use in IBD patients is associated with increased risk of other adverse outcomes, considering the PPI-associated mineral, electrolyte and microbial alterations also needs rigorous evaluation

Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner

Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, Bifidobacterium, is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify Bifidobacterium species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway