title: Digestive fate of dietary carrageenan: Evidence of interference with digestive proteolysis and disruption of gut epithelial function.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Laboratory of Molecular Nutrition, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Lulu
authors.initials: L
authors.lastname: Fahoum
authors.affiliation: Laboratory of Chemistry of Foods and Bioactives, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Alice
authors.initials: A
authors.lastname: Moscovici
authors.affiliation: Laboratory of Chemistry of Foods and Bioactives, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Shlomit
authors.initials: S
authors.lastname: David
authors.affiliation: Pediatric Gastroenterology & Nutrition Institution, , Rambam Medical Center, Haifa, Israel.
authors.forename: Ron
authors.initials: R
authors.lastname: Shaoul
authors.affiliation: Department of Nutrition, Rambam Medical Center, Haifa, Israel.
authors.forename: Geila
authors.initials: G
authors.lastname: Rozen
authors.affiliation: Laboratory of Molecular Nutrition, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Esther G
authors.initials: EG
authors.lastname: Meyron-Holtz
authors.affiliation: Laboratory of Chemistry of Foods and Bioactives, Department of Biotechnology and Food Engineering, Technion - Israel Institute of Technology, Haifa, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Lesmes
mesh_terms: D018938:Caco-2 Cells; D002351:Carrageenan / Q000009:adverse effects* / Q000737:chemistry / Q000493:pharmacokinetics*; D004063:Digestion; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D005503:Food Additives / Q000009:adverse effects / Q000493:pharmacokinetics; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects; D059748:Proteolysis; D023062:Receptors, Interleukin-8A / Q000235:genetics / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D005503:Food Additives; D023062:Receptors, Interleukin-8A; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D002351:Carrageenan
keywords: Carrageenan; Digestive proteolysis; Epithelial tight junctions; Intestinal epithelium; Intestinal inflammation