Commercial whey products promote intestinal barrier function with glycomacropeptide enhanced activity in downregulating bacterial endotoxin lipopolysaccharides (LPS)-induced inflammation in vitro

Food Funct. 2020 Jul 22;11(7):5842-5852. doi: 10.1039/d0fo00487a.

Abstract

Cheese whey contains bioactive compounds which have shown multiple health-promoting benefits. This study aimed to assess the commercial whey products (CWP) whey protein isolate (WPI), galacto-oligosaccharide-whey protein concentrate (GOS-W) and glycomacropeptide (GMP) for their potential to improve intestinal health in vitro using HT29-MTX intestinal goblet and Caco-2 epithelial cells. Results from HT29-MTX culture showed that WPI mitigated reactive oxygen species (ROS) production at a higher extent compared to GOS-W or GMP. However, GMP downregulated the lipopolysaccharide (LPS)-induced TLR-4 inflammatory pathway with the highest potency compared to the other CWP. Biomarkers of epithelial integrity assessed on both cell lines showed tight junction proteins claudin-1, claudin-3, occludin (OCC), and zonula occludens-1 (ZO-1) upregulation by GMP in HT29-MTX (1.33-1.93-fold of control) and in Caco-2 cells (1.56-2.09-fold of control). All CWP increased transepithelial electrical resistance (TEER) in TNF-α challenged Caco-2/HT29-MTX co-culture monolayer (p < 0.05), but only GMP was similar to the positive control TGF-β1, known for its role in promoting epithelial barrier function. The TNF-α-induced co-culture monolayer permeability was prevented at similar levels by all CWP (p < 0.05). In conclusion, CWP may be used as functional food ingredients to protect against intestinal disorders with emphasis on the GMP enhanced anti-inflammatory and intestinal barrier function properties. Further in vivo studies are guaranteed to validate these findings.

MeSH terms

  • Biomarkers
  • Caco-2 Cells
  • Caseins / pharmacology*
  • Cell Survival / drug effects
  • Claudin-3 / genetics
  • Claudin-3 / metabolism
  • Endotoxins / toxicity
  • Gene Expression Regulation
  • HT29 Cells
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / etiology
  • Intestines / drug effects
  • Lipopolysaccharides / toxicity*
  • Occludin / genetics
  • Occludin / metabolism
  • Peptide Fragments / pharmacology*
  • Permeability
  • Reactive Oxygen Species / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Whey / metabolism*
  • Whey Proteins / metabolism*
  • Zonula Occludens-1 Protein / genetics
  • Zonula Occludens-1 Protein / metabolism

Substances

  • Biomarkers
  • Caseins
  • Claudin-3
  • Endotoxins
  • Lipopolysaccharides
  • Occludin
  • Peptide Fragments
  • Reactive Oxygen Species
  • TJP1 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Whey Proteins
  • Zonula Occludens-1 Protein
  • caseinomacropeptide