The prevalence of vancomycin resistant enterococcus (VRE) carrier-state has been increasing in patients of intensive care unit and it would be a public health threat. Different research groups conducted decolonizing VRE with probiotic and the results were controversial. Therefore, a systemic approach to search for the probiotic species capable of decolonizing VRE is necessary. Thus, VRE was co-cultured with ten probiotic species. The fluctuations of each bacterial population were analyzed by 16S rRNA sequencing. Microbial network analysis (MNA) was exploited to identify the most critical species in inhibiting the VRE population. The MNA-selected probiotic cocktail was then validated for its efficacy in inhibiting VRE, decolonizing VRE from Caco-2 cells via three approaches: exclusion, competition, and displacement. Finally, the expression of VRE virulence genes after co-incubation with the probiotic cocktail were analyzed with quantitative real-time PCR (qRT-PCR). The MNA-selected probiotic cocktail includes Bacillus coagulans, Lactobacillus rhamnosus GG, Lactobacillus reuteri, and Lactobacillus acidophilus. This probiotic combination significantly reduces the population of co-cultured VRE and prevents VRE from binding to Caco-2 cells by down-regulating several host-adhesion genes of VRE. Our results suggested the potential of this four-strain probiotic cocktail in clinical application for the decolonization of VRE in human gut.

中文翻译：

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通过微生物网络分析鉴定的益生菌鸡尾酒抑制耐万古霉素的肠球菌的生长，致病性基因表达和宿主细胞定殖。

重症监护病房患者对万古霉素耐药的肠球菌（VRE）携带者的患病率一直在上升，这将对公共健康构成威胁。不同的研究小组使用益生菌对VRE进行了非殖民化研究，结果存在争议。因此，需要一种系统的方法来寻找能够使VRE非定殖的益生菌。因此，VRE与十种益生菌物种共培养。通过16S rRNA测序分析每个细菌种群的波动。利用微生物网络分析（MNA）来识别抑制VRE种群的最关键物种。然后，通过三种方法验证了MNA选择的益生菌混合物在抑制VRE，使Caco-2细胞中VRE非克隆化方面的功效：排斥，竞争和置换。最后，通过定量实时PCR（qRT-PCR）分析与益生菌混合物共孵育后VRE毒力基因的表达。MNA精选的益生菌鸡尾酒包括凝结芽孢杆菌，鼠李糖乳杆菌 GG，罗伊氏乳杆菌和嗜酸乳杆菌。这种益生菌组合可通过下调VRE的几个宿主粘附基因，显着减少共培养VRE的数量，并防止VRE与Caco-2细胞结合。我们的结果表明，这种四株益生菌混合物在临床应用中有可能对人肠VRE进行非殖民化。