在糖缀合物中添加唾液酸（唾液酸化）是糖基化的常见加帽步骤。我们的研究旨在确定整体唾液酸化在肠粘膜稳态中的作用。肠上皮唾液酸化组成性缺失的小鼠（IEC Slc35a1-/-小鼠）和肠上皮唾液酸化诱导性缺失的小鼠（TM-IEC Slc35a1-/-小鼠）生成小鼠），用于通过离体和多组学研究确定总体唾液酸化在肠粘膜稳态中的作用。IEC Slc35a1-/- 小鼠出现轻度自发性微生物依赖性结肠炎。此外，30% 的 IEC Slc35a1-/- 小鼠在 12 个月大时直肠内有自发性肿瘤。与对照组相比，TM-IEC Slc35a1-/- 小鼠对 1% DSS 诱导的急性炎症高度敏感。总唾液酸化的丧失与粪便切片和结肠组织内粘液厚度的减少有关。 TM-IEC Slc35a1-/- 小鼠表现出微生物群的改变，梭状芽胞杆菌增加，这与全球至少 20 个独特类群的丰度减少有关；然而，代谢组学分析并未显示短链脂肪酸水平有任何显着差异。与 WT 同窝小鼠相比，5-氟尿嘧啶 (5-FU) 治疗导致 IEC Slc35a1-/- 小鼠出现更严重的小肠粘膜炎，这与 IEC Slc35a1-/-;Lgr5 中小肠隐窝中 Lgr5 细胞代表性的减少有关-GFP 小鼠。整体唾液酸化的丧失会损害粘液稳定性和干细胞生态位，导致微生物依赖性自发性结肠炎和肿瘤发生。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Addition of sialic acids (sialylation) to glycoconjugates is a common capping step of glycosylation. Our study aims to determine the roles of the overall sialylation in intestinal mucosal homeostasis.Mice with constitutive deletion of intestinal epithelial sialylation (IEC Slc35a1-/- mice) and mice with inducible deletion of sialylation in intestinal epithelium (TM-IEC Slc35a1-/- mice) were generated, which were used to determine the roles of overall sialylation in intestinal mucosal homeostasis by ex vivo and muti-omics studies.IEC Slc35a1-/- mice developed mild spontaneous microbiota-dependent colitis. Additionally, 30% of IEC Slc35a1-/- mice had spontaneous tumors in the rectum over the age of 12 months. TM-IEC Slc35a1-/- mice were highly susceptible to acute inflammation induced by 1% DSS vs controls. Loss of total sialylation was associated with reduced mucus thickness on fecal sections and within colon tissues. TM-IEC Slc35a1-/- mice showed altered microbiota with an increase in Clostridia disporicum, which is associated a global reduction in the abundance of at least 20 unique taxa; however, metabolomic analysis did not show any significant differences in short-chain fatty acid levels. Treatment with 5-fluorouracil (5-FU) led to more severe small intestine mucositis in the IEC Slc35a1-/- mice vs. WT littermates, which was associated with reduced Lgr5+ cell representation in small intestinal crypts in IEC Slc35a1-/-;Lgr5-GFP mice.Loss of overall sialylation impairs mucus stability and the stem cell niche leading to microbiota-dependent spontaneous colitis and tumorigenesis.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.