Chloride-led disruption of the intestinal mucous layer impedes Salmonella invasion: evidence for an 'enteric tear' mechanism

Background/Aims: Methods: The intestinal epithelial layer can switch from a net absorptive state to one of net secretion in the presence of luminal toxins and pathogens. This suggests an innate defence role for regulated secretion of mucus, electrolytes and water. We hypothesised that chloride-led fluid secretion across the mucus-covered intestinal epithelium alters barrier properties by influencing the overlying mucous-gel layer. Results: We demonstrated that chloride-led disruption of the epithelial-associated mucus-gel covering HT29-MTX-E12 (E12) human colonic epithelial monolayers, a goblet-cell like line derived from parental HT29 cells, resulted in reduction of associated mucus as well as a reduction in mucous-gel density and barrier properties. Changes in epithelial secretory state were accompanied by increased water transport, and the resulting loss of gel integrity reduced Salmonella typhimurium invasion of epithelia in both E12 monolayers and of isolated rat ileal mucosae. However, neither chloride secretion nor mucus disruption altered numbers of adhering bacteria. Conclusion: These data suggest a role for chloride led fluid secretion in the shedding of the adherent mucous-gel layer, possibly as a rate-limiting innate defence mechanism, and offer evidence for “enteric tears” in intestinal host defence

Increased intestinal permeability in rats subjected to traumatic frontal lobe percussion brain injury

Background: Dysfunction of the gastrointestinal-(Gl} tracns-a common-occurrence following traumatic brain injury (TBI). We hypothesised that increased intestinal permeability may result from a precisely controlled percussion injury to the exposed brains of anaesthetised rats and that such an effect could be assessed in vitro using excised intestinal mucosae mounted in Ussing chambers. Methods: Following craniotomy over the left medial prefrontal cortex on anaesthetised rats, neurotrauma was produced using a pneumatically-driven impactor on the exposed brain. Control rats were subjected to identical procedures but did not receive an impact. Muscle-stripped rat intestinal ileal and colonic segments were mounted in Ussing chambers within 30 minutes of death. Transepithelial electrical resistance (TEER) and the apparent permeability coefficient (Papp) of[14C)-mannitol were recorded from intestinal tissue for 120 minutes. Histopathology was also carried out to determine any gross morphological changes in the intestine. Results: Ileal and colonic mucosae showed no differences in TEER in ileum or colon ofTBI rats compared to controls. The Papp of mannitol was significantly increased in ilea from rats previously exposed to TBI compared to controls. Histological analysis showed gross changes to 50% of the ileal but not the colonic sections from TBI rats. Conclusion: TBI results in significantly reduced ileal barrier function, most likely mediated by open tight junctions. For patients with acute head injury, this may have implications for subsequent oral absorption of nutrients. Systemic delivery of luminal endotoxins may contribute to multiple organ failure