In-depth study of gastrointestinal motility, intestinal barrier function and secretory function in an irritable bowel syndrome post-inflammatory rat model.

The presence of intestinal barrier dysfunction during 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis in rats has been well described. However, it has not been studied extensively in the post-inflammatory model of irritable bowel syndrome (IBS) in pharmacological research, despite its frequent use. Therefore, we aimed to explore the intestinal barrier function in post-colitis rats in a comprehensive manner. To do so, colitis was induced in Sprague Dawley rats with a TNBS-enema, after which mucosal healing was followed via repeated colonoscopies. In the post-inflammatory phase, intestinal permeability was assessed in vivo by measuring the recovery of creatinine, 4 kDa FITC-dextran or sugars in serum or urine after orogastric gavage. In addition, Ussing chamber and qPCR experiments were performed. Gastrointestinal motility and renal function were assessed as potential confounders of the in vivo assays. Rats reached the post-inflammatory stage 10-14 days after the administration of TNBS. With the exception of an increased recovery of creatinine and changes in the mRNA expression of some tight junction molecules, no profound signs of intestinal barrier dysfunction were found. Gastric emptying was delayed 30 min after administration of Evans blue but not at later timepoints and no effects on gastric emptying were found using the solid bead assay. Renal function was unaltered in post-colitis animals indicating no confounding effects of renal and motility function. Taken together, the intestinal barrier function remains largely uncompromised in this IBS post-inflammatory rat model, with only a slight but significant effect on pore pathway permeability.