Background & Aims Irritable bowel syndrome (IBS) is associated with intestinal dysbiosis and symptoms of IBS develop following gastroenteritis. We aimed to study passage of live bacteria through the colonic epithelium, and determine the role of mast cells and vasoactive intestinal polypeptide (VIP) in barrier regulation in IBS and healthy individuals. Methods Colon biopsies from 32 women with IBS and 15 age-matched healthy women (controls) were mounted in Ussing chambers; we measured numbers of fluorescently labeled Escherichia coli HS and Salmonella typhimurium that passed through from the mucosal side to the serosal side of the tissue. Some biopsies were exposed to agents that block the VIP receptors (VPAC1 and VPAC2) or mast cells. Levels of VIP and tryptase were measured in plasma and biopsy lysates. Number of mast cells and mast cells that express VIP or VIP receptors were quantified by immunofluorescence. Biopsies from an additional 5 patients with IBS and 4 controls were mounted in chambers and Salmonella were added; we studied passage routes through the epithelium by transmission electron microscopy and expression of tight junctions by confocal microscopy Results In colon biopsies from patients with IBS, larger numbers of E coli HS and Salmonella passed through the epithelium than in biopsies from controls (P<.0005). In transmission electron microscopy analyses, bacteria were found to cross the epithelium via only the transcellular route. Bacterial passage was reduced in biopsies from patients with IBS and controls after addition of antibodies against VPACs or ketotifen, which inhibits mast cells. Plasma samples from patients with IBS had higher levels of VIP than plasma samples from controls. Biopsies from patients with IBS had higher levels of tryptase, larger numbers of mast cells, and a higher percentage of mast cells that express VPAC1 than biopsies from controls. In biopsies from patients with IBS, addition of Salmonella significantly reduced levels of occludin; subsequent addition of ketotifen significantly reversed this effect. Conclusions We found that colonic epithelium tissues from patients with IBS have increased translocation of commensal and pathogenic live bacteria, compared with controls. Mechanisms of increased translocation include mast cells and VIP.

The gastrointestinal mucosal surface is lined with epithelial cells representing an effective barrier made up with intercellular junctions that separate the inner and the outer environments, and block the passage of potentially harmful substances. However, epithelial cells are also responsible for the absorption of nutrients and electrolytes, hence a semipermeable barrier is required that selectively allows a number of substances in while keeping others out. To this end, the intestine developed the "intestinal barrier function", a defensive system involving various elements, both intra-and extracellular, that work in a coordinated way to impede the passage of antigens, toxins, and microbial byproducts, and simultaneously preserves the correct development of the epithelial barrier, the immune system, and the acquisition of tolerance against dietary antigens and the intestinal microbiota. Disturbances in the mechanisms of the barrier function favor the development of exaggerated immune responses; while exact implications remain unknown, changes in intestinal barrier function have been associated with the development of inflammatory conditions in the gastrointestinal tract. This review details de various elements of the intestinal barrier function, and the key molecular and cellular changes described for gastrointestinal diseases associated with dysfunction in this defensive mechanism.

We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome.

Background Barrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs). Methods Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA. Results Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P &lt; 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P &lt; 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P &lt; 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P &lt; 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P &lt; 0.0005). Conclusions Results indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.