Abstract：
Ulcerative colitis (UC) is an immune-mediated inflammatory disease that can lead to persistent damage and even cancer without any intervention. Conventional treatments can alleviate UC symptoms but are costly and cause various side effects. Tauroursodeoxycholic acid (TUDCA), a secondary bile acid derivative, possesses anti-inflammatory and cytoprotective properties for various diseases, but its potential therapeutic benefits in UC have not been fully explored. Mice were subjected to colitis induction using 3% dextran sulfate sodium (DSS). The therapeutic effect of TUDCA was evaluated by body weight loss, disease activity index (DAI), colon length, and spleen weight ratio. Tissue pathology was assessed using H&E staining, while the levels of pro-inflammatory and anti-inflammatory cytokines in colonic tissue were quantified via ELISA. Tight junction proteins were detected by immunoblotting and intestinal permeability was assessed using fluorescein isothiocyanate (FITC)-dextran. Moreover, the gut microbiota was profiled using high-throughput sequencing of the 16S rDNA gene. TUDCA alleviated the colitis in mice, involving reduced DAI, attenuated colon and spleen enlargement, ameliorated histopathological lesions, and normalized levels of pro-inflammatory and anti-inflammatory cytokines. Furthermore, TUDCA treatment inhibited the downregulation of intestinal barrier proteins, including zonula occludens-1 and occludin, thus reducing intestinal permeability. The analysis of gut microbiota suggested that TUDCA modulated the dysbiosis in mice with colitis, especially for the remarkable rise in Akkermansia TUDCA exerted a therapeutic efficacy in DSS-induced colitis by reducing intestinal inflammation, protecting intestinal barrier integrity, and restoring gut microbiota balance. SIGNIFICANCE STATEMENT: This study demonstrates the potential therapeutic benefits of Tauroursodeoxycholic acid (TUDCA) in ulcerative colitis. TUDCA effectively alleviated colitis symptoms in mice, including reducing inflammation, restoring intestinal barrier integrity and the dysbiosis of gut microbiota. This work highlights the promising role of TUDCA as a potentially alternative treatment, offering new insights into managing this debilitating condition.
摘要：
背景：溃疡性结肠炎（UC）是一种免疫介导的炎症性疾病，在没有任何干预的情况下可导致持续性损伤甚至癌症。常规治疗可以缓解UC症状，但成本高昂，甚至会引起各种副作用。牛磺熊去氧胆酸(TUDCA),次级胆汁酸衍生物，对各种疾病具有抗炎和细胞保护特性，但其在UC中的潜在治疗益处尚未得到充分探索.方法:使用3%葡聚糖硫酸钠(DSS)对小鼠进行结肠炎诱导。通过体重减轻来评估TUDCA的治疗效果，疾病活动指数（DAI），结肠长度,和脾脏重量比。使用H&E染色评估组织病理学，而结肠组织中促炎和抗炎细胞因子的水平通过酶联免疫吸附测定（ELISA）进行定量。通过免疫印迹检测紧密连接蛋白，并使用异硫氰酸荧光素（FITC）-葡聚糖评估肠通透性。此外，使用16SrDNA基因的高通量测序对肠道微生物群进行了分析.结果：TUDCA减轻小鼠结肠炎，涉及减少DAI，结肠和脾脏肿大减弱，改善组织病理学病变，并使促炎和抗炎细胞因子的水平正常化。此外，TUDCA治疗抑制肠屏障蛋白，包括ZO-1和闭塞蛋白的下调，从而降低肠道通透性。肠道菌群的分析表明，TUDCA调节结肠炎小鼠的生态失调，结论：TUDCA通过减少肠道炎症在DSS诱导的结肠炎中发挥治疗作用，保护肠道屏障的完整性，恢复肠道菌群平衡。意义陈述本研究证明牛磺熊去氧胆酸(TUDCA)在溃疡性结肠炎(UC)中的潜在治疗益处。TUDCA有效缓解小鼠结肠炎症状，包括减少炎症,恢复肠道屏障的完整性和肠道微生物群的生态失调。这项工作突出了TUDCA作为潜在替代治疗的有希望的作用，为管理这种衰弱的状况提供了新的见解。
