Blends of Human Milk Oligosaccharides Confer Intestinal Epithelial Barrier Protection in Vitro

• Published in: Nutrients Vol. 12; no. 10; p. 3047
• Main Authors: Natividad, Jane M, Rytz, Andreas, Keddani, Sonia, Bergonzelli, Gabriela, Garcia-Rodenas, Clara L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05-10-2020; MDPI
• Subjects: Babies; Baby foods; Breast Feeding; Breast milk; Breastfeeding & lactation; Caco-2 Cells; Caco-2:HT29-MTX cultures; Cytokines; Cytotoxicity; Dextran; Dextrans; Female; Fluorescein; Fucose - analysis; HT29 Cells; human milk oligosaccharides; Humans; Inflammation; Inflammatory diseases; intestinal barrier function; Intestinal Mucosa - drug effects; Intestinal Mucosa - physiology; Intestine; Isothiocyanate; Lactose; Lactose - analogs & derivatives; Lactose - analysis; Methotrexate; Microbiota; Milk; Milk, Human - chemistry; Mixtures; Oligosaccharides; Oligosaccharides - administration & dosage; Oligosaccharides - chemistry; Permeability; Permeability - drug effects; Phenols; Pore size; Sialic Acids - analysis; Translocation; Tumor necrosis factor-α; γ-Interferon; United States > US; human milk oligosaccharides; inflammation; intestinal barrier function; Caco-2:HT29-MTX cultures; permeability
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12103047

Breastfeeding is integral in the proper maturation of the intestinal barrier and protection against inflammatory diseases. When human milk (HM) is not available, supplementation with HM bioactives like Human Milk Oligosaccharides (HMOs) may help in providing breastfeeding barrier-protective benefits. An increasing HMO variety is becoming industrially available, enabling approaching the HMO complexity in HM. We aimed at assessing the impact of blends of available HMOs on epithelial barrier function in vitro. The capacity of individual [2'-Fucosyllactose (2'FL), Difucosyllactose, Lacto-N-tetraose, Lacto-N-neotetraose, 3'-Siallylactose and 6'-Siallylactose] or varying combinations of 3, 5 and 6 HMOs to modulate fluorescein-isothiocyanate (FITC)-labelled Dextran 4 KDa (FD4) translocation and/or transepithelial resistance (TEER) was characterized in Caco-2: HT29- methotrexate (MTX) cell line monolayers before and after an inflammatory challenge with TNF-α and IFN-γ. The six HMO blend (HMO6) dose-dependently limited the cytokine-induced FD4 translocation and TEER decrease and increased TEER values before challenge. Similarly, 3 and 5 HMO blends conferred a significant protection against the challenge, with 2'FL, one of the most abundant but most variable oligosaccharides in HM, being a key contributor. Overall, our results suggest differential ability of specific HMOs in modulating the intestinal barrier and support the potential of supplementation with combinations of available HMOs to promote gut health and protect against intestinal inflammatory disorders.