菌剂鸡尾酒疗法，让小鼠抵抗病原微生物感染

Title：
Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium

DOI：
10.1038/NMICROBIOL.2016.215

Abstract：
Protection against enteric infections, also termed colonization resistance, results from mutualistic interactions of the host and its indigenous microbes. The gut microbiota of humans and mice is highly diverse and it is therefore challenging to assign specific properties to its individual members. Here, we have used a collection of murine bacterial strains and a modular design approach to create a minimal bacterial community that, once established in germ-free mice, provided colonization resistance against the human enteric pathogen Salmonella enterica serovar Typhimurium (S. Tm). Initially, a community of 12 strains, termed Oligo-Mouse-Microbiota (Oligo-MM(12)), representing members of the major bacterial phyla in the murine gut, was selected. This community was stable over consecutive mouse generations and provided colonization resistance against S. Tm infection, albeit not to the degree of a conventional complex microbiota. Comparative (meta)genome analyses identified functions represented in a conventional microbiome but absent from the Oligo-MM(12). By genome-informed design, we created an improved version of the Oligo-MM community harbouring three facultative anaerobic bacteria from the mouse intestinal bacterial collection (miBC) that provided conventional-like colonization resistance. In conclusion, we have established a highly versatile experimental system that showed efficacy in an enteric infection model. Thus, in combination with exhaustive bacterial strain collections and systems-based approaches, genome-guided design can be used to generate insights into microbe-microbe and microbe-host interactions for the investigation of ecological and disease-relevant mechanisms in the intestine.

All Authors：
Sandrine Brugiroux,Markus Beutler,Carina Pfann,Debora Garzetti,Hans-Joachim Ruscheweyh,Diana Ring,Manuel Diehl,Simone Herp,Yvonne Lötscher,Saib Hussain,Boyke Bunk,Rüdiger Pukall,Daniel H Huson,Philipp C Münch,Alice C McHardy,Kathy Mccoy,Andrew J Macpherson,Alexander Loy,Thomas Clavel,David Berry,Bärbel Stecher

First Authors：
Sandrine Brugiroux

Correspondence：
Bärbel Stecher

内容要点：

1、利用小鼠肠道菌群中的菌株集合，结合模块化设计方法，创造了一个最小细菌群落；

2、定殖于无菌小鼠体内后，可提供对鼠伤寒沙门氏菌的定殖抗性；

3、首先，从小鼠肠道菌群中选择12个菌株，可连续稳定遗传并提供对鼠伤寒沙门氏菌的定殖抗性，虽然定殖抗性不如传统的更复杂的菌群；

4、通过比较基因组学分析，鉴定出传统菌群具有而12个菌株缺乏的功能，并设计了带有3株兼性厌氧菌的最新的最小细菌群落版本，可提供类似于传统复杂菌群的定殖抗性。