Human Milk Oligosaccharides Differently Modulate Goblet Cells Under Homeostatic, Proinflammatory Conditions and ER Stress

SCOPE: Human milk oligosaccharides (hMOs) have beneficial effects on intestinal barrier function, but the mechanisms of action are not well-understood. Here we study the effects of hMOs on goblet cells, which indicate that some hMOs may enhance mucus barrier function through direct modulation of goblet cell function.

METHODS AND RESULTS: The modulatory effects of 2'-FL, 3-FL, LNT2, and GOS on the expression of goblet cell secretory related genes MUC2, TFF3, RETNLB, and the Golgi-sulfotransferase genes CHST5, and GAL3ST2 of LS174T were determined by real-time quantitative RT-PCR. 3-FL, LNT2, and GOS modulated LS174T gene expression profiles in a dose and time-dependent manner. In addition, the up-regulation of MUC2 was confirmed by immunofluorescence staining. Effects of 2'-FL, 3-FL, LNT2, and GOS on gene transcription of LS174T were also assessed during exposure to TNF-α, IL-13, or tunicamycin. During TNF-α challenge, 3-FL and LNT2 enhanced MUC2 and TFF3 gene expression. After IL-13 exposure, 2'-FL, 3-FL, and LNT2 all showed up-regulating effects on MUC2, 3-FL and LNT2 also enhanced TFF3 expression. LNT2 significantly reversed Tm-induced down-regulating of TFF3, RETNLB, and CHST5.

CONCLUSION: Our findings indicate that hMOs may enhance mucus barrier function through direct modulation of intestinal goblet cells. Effects were structural and stressor-dependent way. This article is protected by copyright. All rights reserved.