Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner.
Bifidobacterium bifidum Enhances the Intestinal Epithelial Tight Junction Barrier and Protects against Intestinal Inflammation by Targeting the Toll-like Receptor-2 Pathway in an NF-κB-Independent Manner.
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DOI：
10.3390/ijms22158070
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发表时间：
2021-07-28
影响因子：
5.6
通讯作者：
Ma TY
中科院分区：
文献类型：
--
作者：
Al-Sadi R;Dharmaprakash V;Nighot P;Guo S;Nighot M;Do T;Ma TY
肠紧密连接（TJ）屏障缺陷是炎症性肠病（IBD）发病机制的标志。迄今为止，还没有针对肠道TJ屏障的有效治疗方法。在各种益生菌中，双歧杆菌是研究最广泛的对肠道TJ屏障有益的细菌之一。本研究的主要目的是鉴定双歧杆菌种类，这些双歧杆菌可引起肠上皮TJ屏障的持续增强，并可用于治疗靶向肠TJ屏障并预防或治疗肠道炎症。我们的研究结果表明，两歧双歧杆菌引起了Caco-2单层肠道TJ屏障的显著、持续增强。两歧双歧杆菌对TJ屏障的作用是菌株特异性的，只有指定为BB1的菌株对TJ屏障功能的增强最大。BB1增强肠道TJ屏障的机制需要活的细菌细胞/肠细胞相互作用，并通过BB1附着于顶端膜表面的toll样受体-2 （TLR-2）介导。BB1对肠上皮TJ屏障功能的增强是通过激活p38激酶通路介导的，而不是NF-κB信号通路。此外，BB1以tlr -2依赖的方式显著增强小鼠肠道TJ屏障，并对右旋糖酐硫酸钠（DSS）诱导的小鼠结肠通透性增加具有保护作用，并以TJ屏障依赖的方式治疗DSS诱导的结肠炎。这些研究表明，益生菌BB1通过附着于肠细胞TLR-2受体复合物和激活p38激酶途径的新机制，引起菌株特异性肠道TJ屏障的增强。
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, Bifidobacterium, 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 Bifidobacterium 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 Bifidobacterium bifidum caused a marked, sustained enhancement in the intestinal TJ barrier in Caco-2 monolayers. The Bifidobacterium bifidum 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.
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影响因子：
24.5
作者：
Furrie, E
通讯作者：
Furrie, E
DOI：
10.1152/ajpgi.00228.2009
发表时间：
2010-07-01
影响因子：
4.5
作者：
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4.4
作者：
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影响因子：
3.7
作者：
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通讯作者：
Pizarro TT