Differential protective effects of whole and skimmed whey on LPS-induced barrier dysfunction and inflammation in Caco-2/TC7 cells

Layunta, Elena (Universidad de Zaragoza) ; García, Laura (Universidad de Zaragoza) ; Gimeno, Sofía (Universidad de Zaragoza) ; Martínez, Jaime (Universidad de Zaragoza) ; Sánchez, Lourdes (Universidad de Zaragoza) ; Gras, Laura (Universidad de Zaragoza)

Resumen: Background: Lipopolysaccharide (LPS) from Gram-negative bacteria disrupts intestinal epithelial integrity and promotes inflammation, contributing to the pathogenesis of gastrointestinal disorders. Dairy-based whey products are rich in bioactive compounds with known barrier-protective and immunomodulatory properties. 
Objective: This study aimed to evaluate the effects of two types of bovine whey — bovine whole whey (BWW) and bovine skimmed whey (BSW) — on LPS-induced barrier dysfunction and inflammation in the intestinal in vitro model Caco-2/TC7 cells. 
Methods: Caco-2/TC7 cell line was exposed to 20 µg/ml LPS for 24h to induce epithelial barrier disruption. Additionally, cells were treated with 5 mg/ml BWW or 5 mg/ml BSW alone, or in combination with 20 µg/ml LPS. Transepithelial electrical resistance (TEER), FITC-dextran permeability, and mRNA expression of tight junction (TJ) proteins (ZO-1, claudin-1, claudin-3, occludin) and inflammation-related genes (IL-1R, COX-2, iNOS) were assessed. 
Results: LPS significantly reduced TEER without increasing macromolecular permeability or altering TJ gene expression. Both whey fractions restored TEER to control levels, with BSW also enhancing baseline barrier integrity. BWW and BSW upregulated ZO-1 and claudin-1 mRNA expression, though claudin-1 was downregulated when BSW was combined with LPS. Importantly, only BWW normalized LPS-induced overexpression of IL-1R, COX-2, and iNOS, indicating better anti-inflammatory properties likely due to its retained lipid components.
Conclusion: Both whey fractions reinforce epithelial barrier function under LPS challenge, but only whole whey (BWW) provides dual protection by also attenuating inflammatory responses. These findings support the potential of whole whey as a functional food ingredient for intestinal health by targeting both physical and immunological aspects of barrier dysfunction.
Keywords: bovine whey, LPS, intestinal permeability, tight junction proteins, inflammation

Idioma: Inglés

DOI: 10.31989/ffhd.v15i11.1774

Año: 2025

Publicado en: Functional Foods in Health and Disease 15, 11 (2025), 867-881
ISSN: 2378-7007

Financiación: info:eu-repo/grantAgreement/ES/DGA/A20-23R
Financiación: info:eu-repo/grantAgreement/ES/MICINN/PID2022-139104OB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Medicina y Cirugía Animal (Dpto. Patología Animal)
Área (Departamento): Área Tecnología de Alimentos (Dpto. Produc.Animal Cienc.Ali.)