Intestinal Epithelial Barrier Dysfunction in Disease and Possible Therapeutical Interventions

Abstract

The intestinal epithelial monolayer constitutes a physical and functional barrier between the organism and the external environment. It regulates nutrients absorption, water and ion fluxes, and represents the first defensive barrier against toxins and enteric pathogens. Epithelial cells are linked together at the apical junctional complex by tight junctions that reduce the extracellular space and the passage of charge entities while forming a physical barrier to lipophilic molecules. Cultured intestinal epithelial cells have been extensively used to study intestinal absorption of newly synthesized drugs and the regulation of tight junctions structure and function. In vitro mild irritants, proinflammatory cytokines, toxins and pathogens, and adverse environmental conditions open tight junctions and increase paracellular permeability, an effect often accompanied by immune activation of the enterocytes. Conversely, inhibition of proinflammatory cytokines, exposure to growth factors and probiotics, among others, exert a protective effect. Impaired barrier function results from activation of signalling pathways that lead to alteration of junctional proteins expression and/or distribution. In vivo, intestinal barrier dysfunction is associated with various intestinal and non-intestinal disorders including inflammatory bowel disease, celiac disease, and diarrhoeal infection. This review will describe the current knowledge of the mechanisms regulating tight junctions and intestinal permeability, how these findings have lead to a better understanding of barrier alteration in human intestinal disorders, and what the emerging therapies to treat these pathologies are.

The Impact of Probiotics on the Gastrointestinal Physiology

“…It regulates nutrients absorption, water and ion fluxes, and represents the first defensive barrier against toxins and enteric pathogens. Intestinal barrier consists of internal and external layers; the internal layer includes intestinal epithelial cells and tight junctions (TJ), the external layer includes bacteria and a mucus layer (Catalioto et al, 2011).…”

Coeliac Disease: From Triggering Factors to Treatment

“…Zonulin is overexpressed in CD and induces an increase in intestinal permeability [25]. Furthermore, the cell adhesion structures are damaged in patients with CD also contributing to the increased mucosal permeability [26].…”

The increase of bioavailability and antiinflammatory effect of indomethacin included into phospholipid nanoparticles

“…Анализ данных последних лет показывает, что такое проникновение повышается со снижением размеров частиц лекарственной формы. [15,18,19]. В модельном эксперименте на Caco-2 клетках нами было показано, что встраивание лекарства в фосфолипидные наночастицы облегчает прохождение индометацина через клеточный монослой [15].…”