A breach in the intestinal permeability as a factor of etiopathogenesis of functional gastrointestinal diseases

To date the mechanisms of etiopathogenesis of functional gastrointestinal diseases continue to be actively studied. By now, alteration of the components of the intestinal epithelial tight junctions supporting the intestinal barrier integrity has been identified in several studies in patients with irritable bowel syndrome and functional dyspepsia (FD). Characteristic changes in patients with IBS compared with healthy controls include decreased expression of ZO-1 protein and occludin in mucosal biopsy specimens from various parts of the colon. On the other hand, the analysis of duodenal biopsy specimens shows similar changes in patients with FD. The causative factor of these changes continues to be studied. In fact, experimental and clinical studies conducted to date have demonstrated that there are factors that affect adversely the structural and functional stability of intestinal tight junctions. Regardless of the initiating factor, the compromise of tight junctions results in the breach of permeability of the intestinal mucosa and the entry of various intraluminal factors into the proper mucous plate, contributing to the activation of resident immunocompetent cells. Due to the production of cytokines and other biologically active substances, the latter lead to sensitization of nerve endings, thereby inducing the development of visceral hypersensitivity phenomenon and alteration of the motor behaviours of the gastrointestinal tract. The literature describes the phenomenon of activation of a local inflammatory response in patients with functional gastrointestinal diseases as “low-grade inflammation”. These data update the need to consider restoration of the intestinal mucosal barrier in patients with diseases in question as a therapeutic target. This review article systematizes data on this problem.

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