Abstract
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.
Highlights
Breastfeeding is the gold standard for infant nutrition [1]
This research further substantiates the key role of Human Milk Oligosaccharides (HMOs) on intestinal barrier homeostasis
Using an in vitro epithelial culture model of barrier dysfunction, we demonstrated that combinations and individual HMOs have differential capacity to modulate the epithelial barrier permeability, and that 20 -Fucosyllactose (20 FL) seems to be a key contributor to the protection of the barrier integrity during an inflammatory insult
Summary
Several mechanisms, including maintenance of intestinal barrier integrity, are proposed to underlie the protective effect of human milk [5]. Human infants have a permeable intestine, which becomes tighter within the first weeks of life [6,7]. Breast-fed infants have a faster evolution rate towards tighter epithelium than formula-fed infants [7,8]. It is not yet clear whether a delayed intestinal barrier maturation has an immediate consequence on infant gut health or may alter intestinal function programming that may, in turn, influence development and future health.
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