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一种合生元对小鼠感染模型中多重耐药鲍曼不动杆菌的保护作用

Protective Effect of a Synbiotic against Multidrug-Resistant Acinetobacter baumannii in a Murine Infection Model.

作者信息

Asahara Takashi, Takahashi Akira, Yuki Norikatsu, Kaji Rumi, Takahashi Takuya, Nomoto Koji

机构信息

Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan

Yakult Central Institute, Yakult Honsha Co., Ltd., Kunitachi, Tokyo, Japan.

出版信息

Antimicrob Agents Chemother. 2016 Apr 22;60(5):3041-50. doi: 10.1128/AAC.02928-15. Print 2016 May.

Abstract

This study investigated the ability of the probiotic Bifidobacterium breve strain Yakult (BbY) to protect against infection, as well as the potentiation of BbY activity by the synbiotic combination of BbY and prebiotic galactooligosaccharides (GOS). The study employed a mouse model of lethal intestinal multidrug-resistant Acinetobacter baumannii (MDRAb) infection. The endogenous intestinal microbiota was disrupted by the administration of multiple antibiotics, causing the loss of endogenous Bifidobacterium Oral infection of these mice with MDRAb resulted in marked growth of this organism. Additional treatment of the infected mice with a sublethal dose of 5-fluorouracil (5-FU) induced systemic invasion by MDRAb and subsequent animal death. The continuous oral administration of BbY increased the survival rate and inhibited the intestinal growth and invasion by MDRAb in the infection model. Disruptions of the intestinal environment and barrier function in the infected mice were attenuated by BbY. Protection against the MDRAb infection was markedly potentiated by a synbiotic combination of BbY and GOS, although GOS by itself did not provide protection. Negative correlations were observed between intestinal MDRAb and BbY counts or acetic acid levels; positive correlations were observed between acetic acid levels and intestinal epithelium expression of tight-junction-related genes. These results demonstrated that the probiotic and synbiotic markedly potentiated protection against fatal intestinal infection caused by a multidrug-resistant bacterium. Probiotics and synbiotics are presumed to provide protection by compensation for the disrupted indigenous populations, thereby maintaining the intestinal environments and barrier functions otherwise targeted during opportunistic infection by MDRAb.

摘要

本研究调查了益生菌短双歧杆菌养乐多菌株(BbY)预防感染的能力,以及BbY与益生元低聚半乳糖(GOS)的合生元组合对BbY活性的增强作用。该研究采用了致死性肠道多重耐药鲍曼不动杆菌(MDRAb)感染的小鼠模型。通过给予多种抗生素破坏内源性肠道微生物群,导致内源性双歧杆菌丧失。用MDRAb对这些小鼠进行口腔感染导致该菌显著生长。用亚致死剂量的5-氟尿嘧啶(5-FU)对感染小鼠进行额外治疗,诱导MDRAb的全身侵袭并导致动物死亡。在感染模型中,持续口服BbY可提高存活率,并抑制MDRAb在肠道中的生长和侵袭。BbY减轻了感染小鼠肠道环境和屏障功能的破坏。尽管GOS本身不能提供保护作用,但BbY与GOS的合生元组合显著增强了对MDRAb感染的保护作用。观察到肠道MDRAb计数与BbY计数或乙酸水平之间呈负相关;乙酸水平与紧密连接相关基因的肠道上皮表达之间呈正相关。这些结果表明,益生菌和合生元显著增强了对多重耐药菌引起的致命性肠道感染的保护作用。推测益生菌和合生元通过补偿被破坏的本土菌群来提供保护,从而维持肠道环境和屏障功能,否则这些功能在MDRAb机会性感染期间会成为目标。

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