ARTICLE FEED & ADDITIVE MAGAZINE February 2026 93 form the zonula occludens, a gasket-like structure that defines the paracellular pathway. Under normal conditions, this pathway permits controlled passage of water and small ions while restricting larger solutes and luminal macromolecules. Barrier selectivity is governed primarily by transmembrane tight junction proteins. Claudins are the principal pore-forming components and determine ion selectivity and paracellular permeability based on isoform expression and junctional organization. Occludin contributes to junctional stability and stress responsiveness by regulating tight junction assembly and maintenance, while tricellulin is concentrated at tricellular junctions where three epithelial cells meet, sealing structurally vulnerable sites that would otherwise permit macromolecule leakage. These proteins are anchored intracellularly to the actin cytoskeleton through adaptor proteins of the zonula occludens family. This cytoskeletal linkage allows tight junctions to respond dynamically to mechanical strain and intracellular signaling but also renders barrier integrity sensitive to cytoskeletal contraction or disorganization. TRANSITION FROM INTESTINAL HOMEOSTASIS TO LEAKY GUT SYNDROME Leaky gut syndrome emerges when oxidative and inflammatory stress disrupt tight junction structure and regulation. Excess reactive oxygen species and reactive nitrogen species (ROS and RNS) are central drivers of this transition. Oxidative and nitrosative stress alter signaling pathways that regulate tight junction protein trafficking, leading to internalization or redistribution of claudins and occludin away from the apical membrane and weakening their anchorage to actin. Concurrently, stress-induced cytoskeletal contraction widens paracellular spaces and compromises junctional cohesion. Disruption of tricellulin localization further increases permeability at tricellular contacts, disproportionately facilitating passage of larger luminal antigens. Once barrier integrity is reduced, food antigens, toxins, and microbial products translocate across the epithelium and activate mucosal immune cells, amplifying inflammatory signaling and ROS production. This self-reinforcing cycle sustains tight junction disruption and perpetuates the leaky gut state. Ions H2O Ions Ions Food antigens Toxins Microbes TJ Zonula occludens Occludin Tricellulin Intestinal Homeostasis Leaky Gut Syndrome TJ disruption Claudin Excess ROS/RNS Antioxidants • NO donor • Glutathione Actin
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