SCOPE: Human milk oligosaccharides (hMOs) can attenuate inflammation by modulating intestinal epithelial cells, but the mechanisms of action are not well-understood. Here we study the effects of hMOs on TNF-α induced inflammatory events in gut epithelial cells.
METHODS AND RESULTS: The modulatory effects of 2'-FL, 3-FL, 6'-SL, LNT, LNnT, LDFT, and LNT2 on immature FHs 74 Int intestinal epithelial cells and on adult T84 intestinal epithelial cells with or without TNF-α exposure were determined. IL-8 secretion in FHs 74 Int and T84 were quantified to determine possible hMO induced attenuation of inflammatory events by ELISA. 3-FL, LNnT, and LDFT significantly attenuated TNF-α induced inflammation in FHs 74 Int, while LNT2 induced IL-8 secretion in T84. In addition, microscale thermophoresis assays and ELISA were used to study the possible mechanisms of interaction between effective hMOs and TNFR1. 3-FL, LNnT, and LDFT exerted TNFR1 ectodomain shedding while LNnT also showed binding affinity to TNFR1 with a Kd of 900 ± 660 nM as measured with microscale thermophoresis.
CONCLUSION: Our findings indicate that specific hMO types attenuate TNF-α induced inflammation in fetal gut epithelial cells through TNFR1 in a hMO structure-dependent fashion suggest possibilities to apply hMOs in management of TNF-α dependent diseases. This article is protected by copyright. All rights reserved.