Laboratory of Microbial Ecology and Technology (LabMET), Ghent University, Ghent, Belgium.
PLoS One. 2012;7(5):e37116. doi: 10.1371/journal.pone.0037116. Epub 2012 May 31.
The probiotic effects of Lactobacillus reuteri have been speculated to partly depend on its capacity to produce the antimicrobial substance reuterin during the reduction of glycerol in the gut. In this study, the potential of this process to protect human intestinal epithelial cells against infection with Salmonella enterica serovar Typhimurium was investigated. We used a three-dimensional (3-D) organotypic model of human colonic epithelium that was previously validated and applied to study interactions between S. Typhimurium and the intestinal epithelium that lead to enteric salmonellosis. Using this model system, we show that L. reuteri protects the intestinal cells against the early stages of Salmonella infection and that this effect is significantly increased when L. reuteri is stimulated to produce reuterin from glycerol. More specifically, the reuterin-containing ferment of L. reuteri caused a reduction in Salmonella adherence and invasion (1 log unit), and intracellular survival (2 log units). In contrast, the L. reuteri ferment without reuterin stimulated growth of the intracellular Salmonella population with 1 log unit. The short-term exposure to reuterin or the reuterin-containing ferment had no observed negative impact on intestinal epithelial cell health. However, long-term exposure (24 h) induced a complete loss of cell-cell contact within the epithelial aggregates and compromised cell viability. Collectively, these results shed light on a potential role for reuterin in inhibiting Salmonella-induced intestinal infections and may support the combined application of glycerol and L. reuteri. While future in vitro and in vivo studies of reuterin on intestinal health should fine-tune our understanding of the mechanistic effects, in particular in the presence of a complex gut microbiota, this the first report of a reuterin effect on the enteric infection process in any mammalian cell type.
鼠李糖乳杆菌的益生菌作用被推测部分依赖于其在肠道内还原甘油时产生抗菌物质雷普汀的能力。在这项研究中，研究了这一过程保护人肠道上皮细胞免受肠炎沙门氏菌感染的潜力。我们使用了先前经过验证的人结肠上皮三维（3-D）器官型模型，并将其应用于研究肠炎沙门氏菌与肠道上皮相互作用导致肠沙门氏菌病的过程。使用这个模型系统，我们表明鼠李糖乳杆菌可以保护肠道细胞免受沙门氏菌早期感染，并且当鼠李糖乳杆菌被刺激从甘油产生雷普汀时，这种作用会显著增强。更具体地说，含有雷普汀的鼠李糖乳杆菌发酵液可减少沙门氏菌的粘附和入侵（1 个对数单位），并减少细胞内存活（2 个对数单位）。相比之下，不含雷普汀的鼠李糖乳杆菌发酵液刺激细胞内沙门氏菌种群生长 1 个对数单位。短期暴露于雷普汀或含雷普汀的发酵液对肠道上皮细胞健康没有观察到负面影响。然而，长期暴露（24 小时）会导致上皮细胞聚集体内的细胞-细胞接触完全丧失，并损害细胞活力。总的来说，这些结果揭示了雷普汀在抑制沙门氏菌引起的肠道感染中的潜在作用，并可能支持甘油和鼠李糖乳杆菌的联合应用。虽然未来关于雷普汀对肠道健康的体外和体内研究应该可以微调我们对其机制作用的理解，特别是在存在复杂肠道微生物群的情况下，但这是雷普汀对任何哺乳动物细胞类型肠道感染过程影响的首次报告。
