PDF(Pubmed)
Abstract：
Circadian rhythm plays an important role in intestinal homeostasis and intestinal immune function. Circadian rhythm dysregulation was reported to induce intestinal microbiota dysbiosis, intestinal barrier disruption, and trigger intestinal inflammation. However, the relationship between intestinal microbiota metabolites and the circadian rhythm of the intestinal barrier was still unclear. Urolithin A (UA), a kind of intestinal microbial metabolite, was selected in this study. Results showed UA influenced on the expression rhythm of the clock genes BMAL1 and PER2 in intestinal epithelial cells. Furthermore, the study investigated the effects of UA on the expression rhythms of clock genes (BMAL1 and PER2) and tight junctions (OCLN, TJP1, and CLND1), all of which were dysregulated by inflammation. In addition, UA pre-treatment by oral administration to female C57BL/6 mice showed the improvement in the fecal IgA concentrations, tight junction expression (Clnd1 and Clnd4), and clock gene expression (Bmal1 and Per2) in a DSS-induced colitis model induced using DSS treatment. Finally, the Nrf2-SIRT1 signaling pathway was confirmed to be involved in UA\'s effect on the circadian rhythm of intestinal epithelial cells by antagonist treatment. This study also showed evidence that UA feeding showed an impact on the central clock, which are circadian rhythms in SCN. Therefore, this study highlighted the potential of UA in treating diseases like IBD with sleeping disorders by improving the dysregulated circadian rhythms in both the intestinal barrier and the SCN.
摘要：
昼夜节律在肠道稳态和肠道免疫功能中起重要作用。据报道，昼夜节律失调会导致肠道微生物群失调，肠屏障破坏，引发肠道炎症.然而,肠道微生物代谢产物与肠道屏障昼夜节律的关系尚不清楚。尿磷脂A(UA),一种肠道微生物代谢产物，在这项研究中被选中。成果显示UA对肠上皮细胞时钟基因BMAL1和PER2的表达节律有影响。此外，该研究调查了UA对时钟基因（BMAL1和PER2）和紧密连接（OCLN，TJP1和CLND1)，所有这些都因炎症而失调。此外,通过口服给予雌性C57BL/6小鼠UA预处理显示粪便IgA浓度的改善，紧密连接表达式(Clnd1和Clnd4)，在使用DSS治疗诱导的DSS诱导的结肠炎模型中和时钟基因表达(Bmal1和Per2)。最后,Nrf2-SIRT1信号通路通过拮抗剂治疗证实参与UA对肠上皮细胞昼夜节律的影响。这项研究还表明，有证据表明，UA喂食对中央时钟有影响，SCN中的昼夜节律。因此,这项研究强调了UA通过改善肠屏障和SCN的昼夜节律失调，在治疗IBD等睡眠障碍疾病方面的潜力。
