Mast Cells Mediate Stress‐Induced Breakdown in Mucosal Barrier Function in a Porcine Model of Irritable Bowel Syndrome

Early weaning stress in the pig triggers lifelong stress sensitivity and intestinal barrier dysfunction similar to Irritable Bowel Syndrome (IBS) in humans. We investigated the role of mast cells (MCs) in stress‐induced intestinal barrier dysfunction in early weaned, IBS model pigs. Piglets were removed from their dams at 17 days of age (Early weaning) and housed in a commercial pig nursery facility. At six weeks postweaning, pigs were subjected to social stress for three hours to induce disturbances in colonic barrier function, measured in terms of transepithelial electrical resistance (TER) and mucosal‐to‐serosal 3 H‐mannitol fluxes in Ussing chambers. To determine the role of MCs in mucosal barrier disturbances, pigs were pretreated, via intraperitoneal injection, with the MC stabilizer agent Cromolyn (20 mg/kg) or saline vehicle prior to stress. Social stress triggered marked reductions in TER (p<0.05) and elevations 3 H‐manntiol flux (p<0.01) compared with unstressed controls indicating impairments in barrier function. Cromolyn inhibited stress‐induced breakdown of mucosal barrier function. In vitro Ussing chamber studies revealed that MC‐mediated colonic barrier disturbances were inhibited by protease inhibitors. These studies show that MCs play a critical role stress‐induced breakdown of mucosal barrier function and that this response is mediated in part by MC proteases.