Paracellular pathway of intestinal epithelium

The paracellular pathway of the intestinal epithelium is the physiological route for the movement of water and solutes through the intercellular spaces between adjacent epithelial cells, a process primarily regulated by the tight junction (TJ) complex (PMID: 23434761). This complex consists of transmembrane proteins such as claudins, occludin, and junctional adhesion molecules (JAMs), which interact with intracellular scaffold proteins like zonula occludens (ZO-1, ZO-2, and ZO-3) to maintain a selective barrier (PMID: 19112140). Under normal conditions, this pathway allows for the absorption of ions and small nutrients while preventing the translocation of larger, potentially harmful luminal contents like pathogens, toxins, and undigested food antigens into the systemic circulation (PMID: 21248165). Dysregulation of the paracellular pathway, often characterized by increased permeability or leaky gut, is strongly associated with the pathogenesis of various conditions, including inflammatory bowel disease (IBD), celiac disease, and type 1 diabetes (PMID: 22731729). Pharmacological targeting of this pathway involves either the use of tight junction modulators, such as larazotide acetate, to restore barrier function in inflammatory states, or the application of permeation enhancers like sodium caprate to transiently increase permeability for the oral delivery of macromolecular drugs (PMID: 26075306). However, therapeutic intervention must be carefully managed to avoid the non-selective entry of luminal toxins, which could exacerbate systemic inflammation or lead to other safety concerns (PMID: 23434761).

Other names

Intestinal paracellular transportTight junction pathwayParacellular barrierIntercellular pathwayTight junction barrier

Modulation of tight junction protein assembly and disassembly to regulate epithelial permeability (PMID: 26075306).