Background  The ability to control uptake across the mucosa and protect from damage of harmful substances from the lumen is defined as intestinal barrier function. A disturbed barrier dysfunction has been described in many human diseases and animal models, for example, inflammatory bowel disease, irritable bowel syndrome, and intestinal hypersensitivity. In most diseases and models, alterations are seen both of the paracellular pathway, via the tight junctions, and of the transcellular routes, via different types of endocytosis. Recent studies of pathogenic mechanisms have demonstrated the important role of neuroimmune interaction with the epithelial cells in the regulation of barrier function. Neural impulses from extrinsic vagal and/or sympathetic efferent fibers or intrinsic enteric nerves influence mucosal barrier function via direct effects on epithelial cells or via interaction with immune cells. For example, by nerve‐mediated activation by corticotropin‐releasing hormone or cholinergic pathways, mucosal mast cells release a range of mediators with effects on transcellular, and/or paracellular permeability (for example, tryptase, TNF‐α, nerve growth factor, and interleukins).

Purpose  In this review, we discuss current physiological and pathophysiological aspects of the intestinal barrier and, in particular, its regulation by neuroimmune factors.