REVIEW article
Front. Drug Deliv.
Sec. Oral Drug Delivery
This article is part of the Research TopicRegulation of Permeability of Tight JunctionsView all 7 articles
Regulation of the Intestinal Permeability of Epithelial Tight Junctions by Food-Derived Molecules
Provisionally accepted
- University College Dublin, Dublin, Ireland
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Controlling TJ permeability in the small intestine facilitates nutrient absorption, maintains luminal osmotic balance, and prevents the paracellular entry of pathogens. The pharmaceutical industry has leveraged the capacity of medium-chain fatty acids and their derivatives to transiently and reversibly open epithelial TJs in formulations to enable oral administration of therapeutic peptides, some of which have received regulatory approval or are progressing in advanced clinical trials. Other food-derived agent including chitosan and its analogues enhance mucoadhesion and also modulate TJ permeability in the intestine. Recently, pelargonidin, a polyphenolic pigment isolated from strawberries, has emerged as a promising food-derived TJ opener, facilitating oral insulin delivery in rat models. Conversely, other food or food-derived molecules reinforce TJ integrity while exerting antioxidant effects, thereby offering potential therapeutic benefits for conditions characterized by increased intestinal permeability including inflammatory bowel disease, sepsis, and coeliac disease. Examples of such agents include the short-chain fatty acid (SCFA), sodium butyrate, various essential and non-essential amino acids, fermented food, the trace element, zinc, and anthocyanins. The exploration of food-derived substances as modulators of intestinal epithelial TJ dynamics is still in its early stages but holds significant promise for future health applications.
Keywords: Butyrate, fermented foods, food-derived bioactive molecules, GI tract, gut microbiome, intestinal epithelial permeability, Intestinal tight junction regulation, Short chain fatty acid
Received: 25 Aug 2025; Accepted: 12 Feb 2026.
Copyright: © 2026 Ryan and Brayden. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Sinead M Ryan
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