Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD.
Intestinal epithelial glycosylation in homeostasis and gut microbiota interactions in IBD.
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DOI：
10.1038/s41575-020-0331-7
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Neish AS
中科院分区：
文献类型：
--
作者：
Kudelka MR;Stowell SR;Cummings RD;Neish AS
炎症性肠病（IBD）影响全球680万人。IBD发病机制涉及多种因素，包括宿主遗传学、免疫失调和肠道微生物群改变。新出现的证据表明肠上皮糖基化是一个未被充分认识的过程，与这三个因素相互作用。IBD与截短的O-聚糖的表达增加以及末端聚糖结构的表达改变相关。IBD基因、糖基转移酶错误定位、改变的糖基转移酶和糖苷酶表达以及生态失调驱动糖组的变化。这些聚糖变化破坏粘液层、聚糖-凝集素相互作用、宿主-微生物相互作用和粘膜免疫，并最终促成IBD发病。上皮聚糖在通过提供细菌配体和营养物调节肠道微生物群并最终决定肠道微生物群的空间组织方面尤其关键。在这篇综述中，我们讨论了肠上皮糖基化的调节，IBD中改变的上皮糖基化，以及这些改变如何促进疾病病理生物学的机制。我们希望这篇综述为今后IBD糖基化研究和IBD聚糖启发疗法的出现提供基础。肠上皮糖基化受宿主遗传学、环境和肠道微生物群的影响。在这篇综述中，Kudelka等人描述了上皮聚糖的功能，并讨论了上皮糖基化在克罗恩病和溃疡性结肠炎中的作用。
Inflammatory bowel disease (IBD) affects 6.8 million people globally. A variety of factors have been implicated in IBD pathogenesis, including host genetics, immune dysregulation and gut microbiota alterations. Emerging evidence implicates intestinal epithelial glycosylation as an underappreciated process that interfaces with these three factors. IBD is associated with increased expression of truncated O-glycans as well as altered expression of terminal glycan structures. IBD genes, glycosyltransferase mislocalization, altered glycosyltransferase and glycosidase expression and dysbiosis drive changes in the glycome. These glycan changes disrupt the mucus layer, glycan–lectin interactions, host–microbe interactions and mucosal immunity, and ultimately contribute to IBD pathogenesis. Epithelial glycans are especially critical in regulating the gut microbiota through providing bacterial ligands and nutrients and ultimately determining the spatial organization of the gut microbiota. In this Review, we discuss the regulation of intestinal epithelial glycosylation, altered epithelial glycosylation in IBD, and mechanisms for how these alterations contribute to disease pathobiology. We hope that this Review provides a foundation for future studies on IBD glycosylation and the emergence of glycan-inspired therapies for IBD. Intestinal epithelial glycosylation is influenced by host genetics, the environment and the gut microbiota. In this Review, Kudelka et al. describe the functions of epithelial glycans and discuss the role of epithelial glycosylation in Crohn’s disease and ulcerative colitis.
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