Galacto-oligosaccharides may directly enhance intestinal barrier function through the modulation of goblet cells

Abstract

SCOPE: Here we have tested the hypothesis that prebiotic galacto-oligosaccharides (GOS) may enhance mucosal barrier function through direct modulation of goblet cell function. METHODS AND RESULTS: Human adenocarcinoma-derived LS174T cells, which exhibit an intestinal goblet cell-like phenotype, were used to examine the non-prebiotic effects of GOS on goblet cell functions. LS174T cells were treated with GOS, and the expression of goblet cell secretory product genes mucin 2 (MUC2), trefoil factor 3 (TFF3), resistin-like molecule beta (RETNLB) and the Golgi-sulfotransferase genes, carbohydrate (N-acetylglucosamine-6-O) sulfotransferase 5 (CHST5) and galactose-3-O-sulfotransferase 2 (GAL3ST2), was determined by real-time quantitative RT-PCR. In addition, the abundance of CHST5, TFF3 and RETNLB was confirmed by Western blot analysis. Following treatment with GOS for 72 h, the expression of MUC2 was significantly upregulated 2-4-fold, CHST5 and RETNLB, 5-7-fold, and TFF3 2-4-fold. Western blot analysis demonstrated increased abundance of RETNLB, TFF3 and CHST5. Addition of the Th2 cytokine IL-13 along with GOS resulted in synergistic induction of RETNLB and CHST5. IL-8 secretion was not affected by GOS treatment, suggesting that the effects of GOS are not mediated through an inflammatory pathway. CONCLUSION: Collectively, the data indicate that GOS may enhance mucosal barrier function through direct stimulation of intestinal goblet cells.