Human Milk Oligosaccharides Differently Modulate Goblet Cells Under Homeostatic, Proinflammatory Conditions and ER
Lianghui Cheng1, Chunli Kong1, Marthe T C Walvoort2
1Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands.
Molecular Nutrition & Food Research
|December 5, 2019
Summary
Human milk oligosaccharides (hMOs) enhance intestinal mucus barrier function by directly modulating goblet cells. Specific hMOs like 3-fucosyllactose and lacto-N-triaose II show structure- and stressor-dependent effects on gene expression.
Area of Science:
- Gastroenterology
- Microbiome Research
- Glycobiology
Background:
- Human milk oligosaccharides (hMOs) are known to benefit intestinal barrier function.
- The precise mechanisms by which hMOs influence the intestinal barrier remain incompletely understood.
- Goblet cells play a crucial role in maintaining the mucus barrier, a key component of intestinal defense.
Purpose of the Study:
- To investigate the direct effects of specific human milk oligosaccharides (hMOs) on intestinal goblet cell function.
- To elucidate how hMOs modulate the expression of genes critical for mucus production and intestinal health.
- To determine if hMOs can counteract stressor-induced disruptions in goblet cell gene expression.
Main Methods:
- Real-time quantitative RT-PCR was used to assess gene expression in LS174T cells.
- Specific hMOs including 2'-fucosyllactose (2'-FL), 3-fucosyllactose (3-FL), lacto-N-triaose II (LNT2), and galacto-oligosaccharides (GOS) were tested.
- Immunofluorescence staining confirmed MUC2 upregulation, and gene expression was evaluated under inflammatory (TNF-α, IL-13) and endoplasmic reticulum stress (tunicamycin) conditions.
Main Results:
- 3-FL, LNT2, and GOS modulated LS174T gene expression in a dose- and time-dependent manner.
- Upregulation of MUC2 gene expression by hMOs was confirmed.
- 3-FL and LNT2 enhanced MUC2 and TFF3 expression during TNF-α challenge; 2'-FL, 3-FL, and LNT2 upregulated MUC2 after IL-13 exposure.
- LNT2 notably reversed tunicamycin-induced downregulation of TFF3, RETNLB, and CHST5.
Conclusions:
- Human milk oligosaccharides (hMOs) can enhance mucus barrier function through direct modulation of intestinal goblet cell activity.
- The observed effects of hMOs on goblet cell gene expression are dependent on the specific oligosaccharide structure.
- hMOs demonstrate stressor-dependent effects, suggesting a role in mitigating intestinal challenges.
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