Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education and Tianjin, College of Biotechnology, Tianjin University of Science and Technology, 300457, China. Tianjin Engineering Research Center of Microbial Metabolism and Fermentation Process Control, Tianjin 300457, China.
Pathog Dis. 2020 Mar 1;78(2). doi: 10.1093/femspd/ftaa016.
Intestinal mucosal barriers help the body resist many intestinal inflammatory diseases, such as inflammatory bowel disease (IBD). In this study, we identified a novel bacterium promoting the repair of intestinal mucosa and investigated the potential mechanisms underlying its activity. Culture supernatant of Bacillus subtilis RZ001 upregulated the expression of mucin 2 (MUC2) and tight junction (TJ) proteins in HT-29 cells in vitro. Oral administration of B. subtilis RZ001 may have significantly reduced symptoms such as the dextran sulfate sodium (DSS)-induced decrease in body weight, shortening of colon length and overproduction of proinflammatory factors. The number of goblet cells and levels of MUC2 and TJ proteins were significantly increased in adult mice fed with B. subtilis RZ001. B. subtilis RZ001 cells upregulated the levels of MUC2 in the intestinal organoids. Furthermore, culture supernatant of B. subtilis RZ001 could suppress the Notch signalling pathway and activate the expression of atonal homolog 1 (Atoh1). The transcription factor Atoh1 is required for intestinal secretory cell differentiation and activates transcription of MUC2 via binding to E-boxes on the MUC2 promoter. Taken together, B. subtilis strain RZ001 has the potential for treating IBD. The present study is helpful to elucidate the mechanisms of B. subtilis action.
肠道黏膜屏障有助于机体抵抗多种肠道炎症性疾病，如炎症性肠病（IBD）。在这项研究中，我们鉴定了一种促进肠道黏膜修复的新型细菌，并研究了其活性的潜在机制。枯草芽孢杆菌 RZ001 的培养上清液可在体外上调 HT-29 细胞中黏蛋白 2（MUC2）和紧密连接（TJ）蛋白的表达。枯草芽孢杆菌 RZ001 的口服给药可能显著减轻了葡聚糖硫酸钠（DSS）诱导的体重下降、结肠缩短和促炎因子过度产生等症状。与对照组相比，用枯草芽孢杆菌 RZ001 喂养的成年小鼠的杯状细胞数量以及 MUC2 和 TJ 蛋白水平显著增加。枯草芽孢杆菌 RZ001 细胞可上调肠道类器官中的 MUC2 水平。此外，枯草芽孢杆菌 RZ001 的培养上清液可抑制 Notch 信号通路并激活同源异型盒基因 1（Atoh1）的表达。转录因子 Atoh1 是肠道分泌细胞分化所必需的，可通过结合 MUC2 启动子上的 E 盒激活 MUC2 的转录。综上所述，枯草芽孢杆菌 RZ001 菌株具有治疗 IBD 的潜力。本研究有助于阐明枯草芽孢杆菌作用的机制。
