Outer Membrane Vesicles and Soluble Factors Released by Probiotic Escherichia coli Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells.
Outer Membrane Vesicles and Soluble Factors Released by Probiotic Escherichia coli Nissle 1917 and Commensal ECOR63 Enhance Barrier Function by Regulating Expression of Tight Junction Proteins in Intestinal Epithelial Cells.
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DOI：
10.3389/fmicb.2016.01981
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发表时间：
2016
影响因子：
5.2
通讯作者：
Baldomà L
中科院分区：
文献类型：
--
作者：
Alvarez CS;Badia J;Bosch M;Giménez R;Baldomà L
胃肠道上皮层形成物理和生化屏障，维持宿主和肠道微生物群之间的隔离。这种屏障的完整性对于维持体内稳态至关重要，其功能障碍与多种疾病有关，特别是炎症性肠病。肠道微生物，特别是益生菌，通过降低肠道通透性和加强紧密连接来调节屏障完整性。益生菌大肠杆菌Nissle 1917（EcN）是人类肠道的良好定殖者，在人类溃疡性结肠炎的缓解中具有经证实的治疗功效。EcN通过上调和重新分布紧密连接蛋白ZO-1、ZO-2和claudin-14积极调节肠上皮屏障。紧密连接蛋白-14的上调归因于分泌蛋白TcpC。ZO-1和ZO-2的调节是否由EcN分泌因子介导仍不清楚。本研究的目的是探讨是否外膜囊泡（OMV）释放的EcN加强上皮屏障。本研究包括其他E.含有tcpC基因的人肠道来源的大肠杆菌菌株，如ECOR 63。将从野生型菌株和衍生的tcpC突变体收集的无细胞上清液分级分离成分离的OMV和可溶性分泌因子。这些细胞外组分对上皮屏障的影响通过测量跨上皮阻力和T-84和Caco-2极化单层中几种紧密连接蛋白的表达来评价。我们的研究结果表明，EcN和ECOR 63的增强活性并不完全依赖于TcpC。由这些菌株分泌的OMV和可溶性因子都促进ZO-1和密蛋白-14的上调以及密蛋白-2的下调。OMV介导的作用是TcpC独立的。可溶性分泌的TcpC有助于上调ZO-1和claudin-14，但这种蛋白质对claudin-2的转录调控没有影响。因此，除了OMV和TcpC之外，由这些微生物群菌株释放的其他活性因子有助于上皮屏障的增强。
The gastrointestinal epithelial layer forms a physical and biochemical barrier that maintains the segregation between host and intestinal microbiota. The integrity of this barrier is critical in maintaining homeostasis in the body and its dysfunction is linked to a variety of illnesses, especially inflammatory bowel disease. Gut microbes, and particularly probiotic bacteria, modulate the barrier integrity by reducing gut permeability and reinforcing tight junctions. Probiotic Escherichia coli Nissle 1917 (EcN) is a good colonizer of the human gut with proven therapeutic efficacy in the remission of ulcerative colitis in humans. EcN positively modulates the intestinal epithelial barrier through upregulation and redistribution of the tight junction proteins ZO-1, ZO-2 and claudin-14. Upregulation of claudin-14 has been attributed to the secreted protein TcpC. Whether regulation of ZO-1 and ZO-2 is mediated by EcN secreted factors remains unknown. The aim of this study was to explore whether outer membrane vesicles (OMVs) released by EcN strengthen the epithelial barrier. This study includes other E. coli strains of human intestinal origin that contain the tcpC gene, such as ECOR63. Cell-free supernatants collected from the wild-type strains and from the derived tcpC mutants were fractionated into isolated OMVs and soluble secreted factors. The impact of these extracellular fractions on the epithelial barrier was evaluated by measuring transepithelial resistance and expression of several tight junction proteins in T-84 and Caco-2 polarized monolayers. Our results show that the strengthening activity of EcN and ECOR63 does not exclusively depend on TcpC. Both OMVs and soluble factors secreted by these strains promote upregulation of ZO-1 and claudin-14, and down-regulation of claudin-2. The OMVs-mediated effects are TcpC-independent. Soluble secreted TcpC contributes to the upregulation of ZO-1 and claudin-14, but this protein has no effect on the transcriptional regulation of claudin-2. Thus, in addition to OMVs and TcpC, other active factors released by these microbiota strains contribute to the reinforcement of the epithelial barrier.
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