PDF(Pubmed)
Abstract：
The gut microbiome is a significant factor in the pathophysiology of ulcerative colitis (UC), prompting investigations into the use of probiotic therapies to counter gastrointestinal inflammation. However, while much attention has been given to the therapeutic potential of microbes at the species and strain level, the discovery and application of their metabolic products may offer more precise and controlled solutions in battling disease. In this work, we examined the therapeutic potential of indole lactic acid (ILA) to alleviate inflammation in a murine model of colitis. A previously constructed ILA-producing Escherichia coli Nissle 1917 strain (EcN aldh) and its isogenic non-ILA producing counterpart (EcN) were studied in a murine model of Dextran Sodium Sulfate (DSS) induced colitis. The colitic animals suffered from severe colitic symptoms, with no differentiation between the groups in body weight loss and disease activity index. However, three days after cessation of DSS treatment the EcN aldh-treated mice showed signs of reduced intestinal inflammation, as manifested by lower concentrations of fecal lipocalin-2. Additionally, expression analysis of the inflamed tissue revealed distinct effects of the EcN aldh strain on proteins associated with intestinal health, such as TFF3, occludin and IL-1β expression. These results show no impact of EcN or EcN aldh on acute DSS-induced colitis, but suggest that in particular EcN aldh may assist recovery from intestinal inflammation.
摘要：
肠道微生物群是溃疡性结肠炎（UC）病理生理学的重要因素，促使研究使用益生菌疗法来对抗胃肠道炎症。然而,尽管人们对微生物在物种和菌株水平上的治疗潜力给予了很多关注，它们代谢产物的发现和应用可能为抗击疾病提供更精确和可控的解决方案。在这项工作中,在小鼠结肠炎模型中,我们研究了吲哚乳酸(ILA)缓解炎症的治疗潜力.在葡聚糖硫酸钠（DSS）诱导的结肠炎的小鼠模型中研究了先前构建的生产ILA的大肠杆菌Nissle1917菌株（EcNaldh）及其等基因非ILA生产对应物（EcN）。结肠动物有严重的结肠症状，两组之间在体重减轻和疾病活动指数方面没有区别。然而,停止DSS治疗三天后，EcNaldh治疗的小鼠表现出肠道炎症减少的迹象，表现为较低浓度的粪便脂质运载蛋白-2。此外,发炎组织的表达分析揭示了EcNaldh菌株对与肠道健康相关的蛋白质的不同作用，如TFF3、occludin和IL-1β表达。这些结果表明EcN或EcNaldh对急性DSS诱导的结肠炎没有影响，但建议特别是EcNaldh可能有助于肠道炎症的恢复。
