Food-derived molecules as regulators of intestinal tight junctions and barrier function: mechanisms and implications

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.