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Establishing causality in Salmonella-microbiota-host interaction: The use of gnotobiotic mouse models and synthetic microbial communities
International Journal of Medical Microbiology ( IF 4.5 ) Pub Date : 2021-03-02 , DOI: 10.1016/j.ijmm.2021.151484
Bärbel Stecher

Colonization resistance (CR), the ability to block infections by potentially harmful microbes, is a fundamental function of host-associated microbial communities and highly conserved between animals and humans. Environmental factors such as antibiotics and diet can disturb microbial community composition and thereby predispose to opportunistic infections. The most prominent is Clostridioides difficile, the causative agent of diarrhea and pseudomembranous colitis. In addition, the risk to succumb to infections with genuine human enteric pathogens like nontyphoidal Salmonella (NTS) is also increased by a low-diverse, diet or antibiotic-disrupted microbiota. Despite extensive microbial community profiling efforts, only a limited set of microorganisms have been causally linked with protection against enteric pathogens. Furthermore, it remains a challenge to predict colonization resistance from complex microbiome signatures due to context-dependent action of microorganisms. In the past decade, the study of NTS infection has led to the description of several fundamental principles of microbiota-host-pathogen interaction. In this review, I will give an overview on the current state of knowledge in this field and outline experimental approaches to gain functional insight to the role of specific microbes, functions and metabolites in Salmonella-microbiota-host interaction. In particular, I will highlight the value of mouse infection models, which, in combination with culture collections, synthetic communities and gnotobiotic models have become essential tools to screen for protective members of the microbiota and establishing causal relationship and mechanisms in infection research.



中文翻译:

沙门氏菌-微生物群-宿主相互作用中建立因果关系:gnotobiotic小鼠模型和合成微生物群落的使用

抗殖民能力(CR)是阻止潜在有害微生物感染的能力,是宿主相关微生物群落的基本功能,在动物和人类之间高度保守。环境因素(例如抗生素和饮食)可能会干扰微生物群落的组成,从而容易引发机会性感染。最突出的是艰难梭状芽胞杆菌,是腹泻和假膜性结肠炎的病原体。此外,屈服于真正的人类肠道病原体(如非伤寒沙门氏菌)感染的风险低多样性,饮食或受抗生素破坏的微生物群也会增加(NTS)。尽管对微生物群落进行了广泛的研究,但是只有有限的一组微生物与针对肠道病原体的保护作用存在因果关系。此外,由于微生物的背景依赖性作用,根据复杂的微生物组特征来预测定植抗性仍然是一个挑战。在过去的十年中,对NTS感染的研究导致了微生物群-宿主-病原体相互作用的几个基本原理的描述。在这篇综述中,我将概述该领域的当前知识水平,并概述实验方法,以功能洞察特定微生物,功能和代谢物在沙门氏菌中的作用-微生物群与宿主的相互作用。特别是,我将重点介绍小鼠感染模型的价值,该模型与培养物,合成群落和gnotobiotic模型相结合已成为筛选微生物群保护成员并建立感染研究的因果关系和机制的重要工具。

更新日期:2021-03-21
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