PDF(Pubmed)
Abstract：
Maintaining the mucus layer is crucial for the innate immune system. Urolithin A (Uro A) is a gut microbiota-derived metabolite; however, its effect on mucin production as a physical barrier remains unclear. This study aimed to elucidate the protective effects of Uro A on mucin production in the colon. In vivo experiments employing wild-type mice, NF-E2-related factor 2 (Nrf2)-deficient mice, and wild-type mice treated with an aryl hydrocarbon receptor (AhR) antagonist were conducted to investigate the physiological role of Uro A. Additionally, in vitro assays using mucin-producing cells (LS174T) were conducted to assess mucus production following Uro A treatment. We found that Uro A thickened murine colonic mucus via enhanced mucin 2 expression facilitated by Nrf2 and AhR signaling without altering tight junctions. Uro A reduced mucosal permeability in fluorescein isothiocyanate-dextran experiments and alleviated dextran sulfate sodium-induced colitis. Uro A treatment increased short-chain fatty acid-producing bacteria and propionic acid concentration. LS174T cell studies confirmed that Uro A promotes mucus production through the AhR and Nrf2 pathways. In conclusion, the enhanced intestinal mucus secretion induced by Uro A is mediated through the actions of Nrf-2 and AhR, which help maintain intestinal barrier function.
摘要：
保持粘液层对于先天免疫系统至关重要。尿石素A（UroA）是一种肠道微生物来源的代谢产物；然而，其作为物理屏障对粘蛋白产生的影响尚不清楚。本研究旨在阐明UroA对结肠粘蛋白产生的保护作用。使用野生型小鼠的体内实验，NF-E2相关因子2（Nrf2）缺陷小鼠，和用芳香烃受体（AhR）拮抗剂治疗的野生型小鼠进行研究UroA的生理作用。进行使用产粘蛋白细胞(LS174T)的体外测定以评估UroA处理后的粘液产生。我们发现UroA通过Nrf2和AhR信号传导促进的粘蛋白2表达增强而增厚小鼠结肠粘液，而不改变紧密连接。UroA降低异硫氰酸荧光素-葡聚糖实验中的粘膜通透性并减轻葡聚糖硫酸钠诱导的结肠炎。UroA处理增加了产生短链脂肪酸的细菌和丙酸浓度。LS174T细胞研究证实UroA通过AhR和Nrf2途径促进粘液产生。总之,UroA诱导的增强的肠粘液分泌是通过Nrf-2和AhR的作用介导的，有助于维持肠道屏障功能。
