4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece; 2nd Department of Propaedeutic Surgery, University of Athens, Medical School, Athens, Greece.
4th Department of Internal Medicine, University of Athens, Medical School, Athens, Greece.
Int J Antimicrob Agents. 2015 Apr;45(4):376-84. doi: 10.1016/j.ijantimicag.2014.11.013. Epub 2015 Jan 6.
Based on several randomised clinical studies indicating benefit from oral probiotic intake for the prevention of hospital-acquired infections in critically ill patients, this study aimed to explain the mechanism of action of probiotics for the prevention of lethal experimental infection by multidrug-resistant (MDR) Pseudomonas aeruginosa. Experiments using an Escherichia coli strain susceptible to all antimicrobials were also conducted. C57BL/6 mice were pre-treated intraperitoneally with sterile water for injection or Lactobacillus plantarum. Survival was recorded and mice were sacrificed for measurement of apoptosis and tissue bacterial overgrowth and for isolation and culture of splenocytes for cytokine production. Experiments were repeated after pre-treatment with a commercial preparation of four probiotics (L. plantarum, Lactobacillus acidophilus, Saccharomyces boulardii and Bifidobacterium lactis; LactoLevure(®)). Peripheral blood mononuclear cells (PBMCs) of healthy volunteers were stimulated by heat-killed P. aeruginosa following pre-treatment with medium or probiotics. Pre-treatment with L. plantarum significantly prolonged survival after challenge by either MDR P. aeruginosa (66.7% vs. 31.3%; P=0.026) or E. coli (56.0% vs. 12.0%, P=0.003). Survival benefit was even more pronounced when mice were pre-treated with LactoLevure(®). Tissue bacterial outgrowth and apoptosis of white blood cells and splenocytes were not altered. TNFα and IL-10 production by splenocytes of mice pre-treated with probiotic was increased and IFNγ production was decreased. Pre-treatment with LactoLevure(®) restored production of IL-17. Stimulation of human PBMCs after probiotic pre-treatment was accompanied by reduced gene expression of SOCS3. The results suggest that the protective effect of probiotics is mediated through prevention of sepsis-induced immunosuppression.
基于几项随机临床试验表明，口服益生菌摄入可预防重症患者医院获得性感染，本研究旨在解释益生菌预防多药耐药（MDR）铜绿假单胞菌致死性实验感染的作用机制。还进行了使用对所有抗生素敏感的大肠杆菌菌株的实验。C57BL/6 小鼠先用无菌注射用水或植物乳杆菌经腹腔预处理。记录存活情况，并对小鼠进行安乐死，以测量细胞凋亡和组织细菌过度生长，并分离和培养脾细胞以产生细胞因子。在使用四种益生菌（植物乳杆菌、嗜酸乳杆菌、布拉氏酵母菌和乳双歧杆菌；LactoLevure®）的商业制剂预处理后重复进行实验。健康志愿者的外周血单核细胞（PBMCs）在用热灭活铜绿假单胞菌刺激前，先用培养基或益生菌预处理。用植物乳杆菌预处理后，用 MDR 铜绿假单胞菌（66.7% vs. 31.3%；P=0.026）或大肠杆菌（56.0% vs. 12.0%，P=0.003）攻击后，存活时间明显延长。当用 LactoLevure®预处理时，生存获益更为显著。组织细菌过度生长和白细胞和脾细胞凋亡没有改变。用益生菌预处理的小鼠脾细胞中 TNFα和 IL-10 的产生增加，IFNγ的产生减少。用 LactoLevure®预处理可恢复 IL-17 的产生。用益生菌预处理后，刺激人 PBMCs，SOCS3 的基因表达减少。结果表明，益生菌的保护作用是通过预防脓毒症引起的免疫抑制来介导的。
