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

Abstract

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

Methods and results: The modulatory effects of 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-triaose II (LNT2), and galacto-oligosaccharides (GOS) on the expression of goblet cell secretory related genes MUC2, TFF3, and RETNLB, and the Golgi-sulfotransferase genes CHST5 and GAL3ST2 of LS174T are 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 upregulation of MUC2 is confirmed by immunofluorescence staining. Effects of 2'-FL, 3-FL, LNT2, and GOS on gene transcription of LS174T are also assessed during exposure to TNF-α, IL-13, or tunicamycin. During TNF-α challenge, 3-FL and LNT2 enhance MUC2 and TFF3 gene expression. After IL-13 exposure, 2'-FL, 3-FL, and LNT2 all show upregulating effects on MUC2; 3-FL and LNT2 also enhance TFF3 expression. LNT2 significantly reverses Tm-induced downregulation of TFF3, RETNLB, and CHST5.

Conclusion: The findings indicate that hMOs may enhance mucus barrier function through direct modulation of intestinal goblet cells. Effects are structure- and stressor-dependent.

Keywords: ER-stress; goblet cells; human milk oligosaccharides; inflammatory condition; mucus barrier.