Abstract：
Ulcerative colitis (UC) is a chronic recurrent inflammatory illness of the gastrointestinal system. The purpose of this study was to explore the alleviating effect of vitamin K2 (VK2) on UC, as well as its mechanism. C57BL/6J mice were given 3% DSS for seven days to establish UC, and they then received VK2 (15, 30, or 60 mg/kg·bw) and 5-aminosalicylic acid (100 mg/kg·bw) for two weeks. We recorded the clinical signs, body weights, colon lengths, and histological changes during the experiment. We detected the inflammatory factor expressions using enzyme-linked immunosorbent assay (ELISA) kits, and we detected the tight junction proteins using Western blotting. We analyzed the intestinal microbiota alterations and short-chain fatty acids (SCFAs) using 16S rRNA sequencing and targeted metabolomics. According to the results, VK2 restored the colon lengths, improved the colonic histopathology, reduced the levels of proinflammatory cytokines (such as IL-1β, TNF-α, and IL-6), and boosted the level of the immunosuppressive cytokine IL-10 in the colon tissues of the colitis mice. Moreover, VK2 promoted the expression of mucin and tight junction proteins (such as occludin and zonula occludens-1) in order to preserve the intestinal mucosal barrier function and prevent UC in mice. Additionally, after the VK2 intervention, the SCFAs and SCFA-producing genera, such as Eubacterium_ruminantium_group and Faecalibaculum, were elevated in the colon. In conclusion, VK2 alleviated the DSS-induced colitis in the mice, perhaps by boosting the dominant intestinal microflora, such as Faecalibaculum, by reducing intestinal microflora dysbiosis, and by modulating the expression of SCFAs, inflammatory factors, and intestinal barrier proteins.
摘要：
溃疡性结肠炎（UC）是胃肠道系统的慢性复发性炎症性疾病。目的探讨维生素K2(VK2)对UC的缓解作用,以及它的机制。C57BL/6J小鼠给予3%DSS7天建立UC,然后他们接受VK2（15、30或60mg/kg·bw）和5-氨基水杨酸（100mg/kg·bw）两周。我们记录了临床症状,体重,结肠长度,以及实验过程中的组织学变化。我们使用酶联免疫吸附试验（ELISA）试剂盒检测炎症因子的表达，我们用蛋白质印迹法检测了紧密连接蛋白。我们使用16SrRNA测序和靶向代谢组学分析了肠道微生物群改变和短链脂肪酸（SCFA）。根据结果,VK2恢复了结肠长度，改善结肠组织病理学，降低促炎细胞因子(如IL-1β，TNF-α,和IL-6），并提高结肠炎小鼠结肠组织中免疫抑制细胞因子IL-10的水平。此外，VK2促进粘蛋白和紧密连接蛋白（如闭塞蛋白和闭塞带1）的表达，以保护小鼠肠粘膜屏障功能并预防UC。此外,在VK2干预之后，SCFA和产生SCFA的属，如肠杆菌和粪杆菌，在结肠中升高。总之,VK2减轻了DSS诱导的小鼠结肠炎，也许是通过促进主要的肠道菌群，例如Faecalibaculum,通过减少肠道微生物菌群失调，通过调节SCFA的表达，炎症因子，和肠道屏障蛋白。
