Digestive fate of dietary carrageenan: Evidence of interference with digestive proteolysis and disruption of gut epithelial function

Scope: The objective of this study was to interrogate two mechanisms by which commercial Carrageenans (E407) (CGN) may adversely affect human health: (i) Through modification of gastric proteolysis and (ii) Through affecting gut epithelial structure and function. Methods and results: Three commercial CGN samples with distinct zeta-potentials (stable at the pH range of 3-7 and varied with physiological levels of CaCl2) were mixed with milk, soy or egg protein isolates, then subjected to a semi-dynamic in vitro digestion model and analyzed by SDS-PAGE. This revealed varying levels of interference with gastric digestive proteolysis and a significant decrease in pepsin activity. Further, a Caco-2 cell model was used to explore various effects of physiologically digested CGN (pdCGN) on various epithelial cell functions and characteristics. Samples of pdCGN (0.005-0.5 mg/mL) affected the epithelial barrier function, including redistribution of the tight-junction protein Zonula Occludens (Zo)-1, changes in cellular F-actin architecture and increased monolayer permeability to the transfer of macromolecules. Moreover, pdCGN induced elevation in the levels of the pro-inflammatory IL-8 receptor CXCR1. Conclusion: This work raises the possibility that CGN may reduce protein and peptide bioaccessibility, disrupt normal epithelial function, promote intestinal inflammation, and consequently compromise consumer health.