Department of Medicine, Penn State College of Medicine, Hershey Medical Center, Penn State University, Hershey, PA 17033, USA.
Int J Mol Sci. 2021 Jul 28;22(15):8070. doi: 10.3390/ijms22158070.
Defective intestinal tight junction (TJ) barrier is a hallmark in the pathogenesis of inflammatory bowel disease (IBD). To date, there are no effective therapies that specifically target the intestinal TJ barrier. Among the various probiotic bacteria, , is one of the most widely studied to have beneficial effects on the intestinal TJ barrier. The main purpose of this study was to identify species that cause a sustained enhancement in the intestinal epithelial TJ barrier and can be used therapeutically to target the intestinal TJ barrier and to protect against or treat intestinal inflammation. Our results showed that caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The effect on TJ barrier was strain-specific, and only the strain designated as BB1 caused a maximal enhancement in TJ barrier function. The mechanism of BB1 enhancement of intestinal TJ barrier required live bacterial cell/enterocyte interaction and was mediated by the BB1 attachment to Toll-like receptor-2 (TLR-2) at the apical membrane surface. The BB1 enhancement of the intestinal epithelial TJ barrier function was mediated by the activation of the p38 kinase pathway, but not the NF-κB signaling pathway. Moreover, the BB1 caused a marked enhancement in mouse intestinal TJ barrier in a TLR-2-dependent manner and protected against dextran sodium sulfate (DSS)-induced increase in mouse colonic permeability, and treated the DSS-induced colitis in a TJ barrier-dependent manner. These studies show that probiotic bacteria BB1 causes a strain-specific enhancement of the intestinal TJ barrier through a novel mechanism involving BB1 attachment to the enterocyte TLR-2 receptor complex and activation of p38 kinase pathway.
肠紧密连接（TJ）屏障缺陷是炎症性肠病（IBD）发病机制的一个标志。迄今为止，尚无专门针对肠 TJ 屏障的有效治疗方法。在各种益生菌中， 是研究最多的对肠 TJ 屏障具有有益影响的一种。本研究的主要目的是鉴定出能持续增强肠上皮 TJ 屏障的 种，可用于治疗肠 TJ 屏障，预防或治疗肠道炎症。我们的结果表明， 在 Caco-2 单层细胞中可显著、持续地增强肠 TJ 屏障。 对 TJ 屏障的作用具有菌株特异性，只有被指定为 BB1 的菌株才能最大程度地增强 TJ 屏障功能。BB1 增强肠 TJ 屏障的机制需要活细菌细胞/肠细胞相互作用，并通过 BB1 在顶端膜表面与 Toll 样受体-2（TLR-2）的附着介导。BB1 增强肠上皮 TJ 屏障功能是通过激活 p38 激酶途径介导的，而不是 NF-κB 信号通路。此外，BB1 以 TLR-2 依赖性方式显著增强小鼠肠 TJ 屏障，并防止葡聚糖硫酸钠（DSS）诱导的小鼠结肠通透性增加，以 TJ 屏障依赖性方式治疗 DSS 诱导的结肠炎。这些研究表明，益生菌 BB1 通过一种涉及 BB1 与肠细胞 TLR-2 受体复合物结合和激活 p38 激酶途径的新机制，特异性增强肠 TJ 屏障。
