Designing mouse gut microbiota community based on bacterial genes leads to enhanced colonization resistance

Mutualistic interactions between host and commensal microbiota have a pivotal role in colonization resistance (CR), protection against infections by enteric pathogens such as Salmonella spp. Previous research supporting this idea includes a study of the commensal bacterium Enterococcus faecium found in the mammals’ intestines that may improve host intestinal barrier function and limit the pathogenesis of infections caused by Salmonella enterica Typhimurium (S. Typhimurium) and Clostridium difficile. However, due to complexity of the gut microbiota the underlying mechanisms of CR are still poorly understood.

A recent study, led by Dr. Bärbel Stecher from the Max von Pettenkofer Institute of Hygiene and Medical Microbiology at Ludwig-Maximilians-University of Munich (Germany), has found that designing a bacterial community based on functional potential may be an effective way of improving health in animal models. The researchers began with a collection of murine bacterial strains and, using a genome-guided approach, created a minimal bacterial community that, once established in germ-free mice, was successful in providing CR against the human enteric pathogen S. Typhimurium.

First, researchers selected a community of 12 bacterial strains, termed Oligo-Mouse-Microbiota (Oligo-MM¹²), that represented members of the major bacterial phyla in the murine gut. Although this bacterial consortium stably colonized mice and was vertically transmitted across filial generations, transplantation of the Oligo-MM¹² consortium only conferred partial protection against oral S. Typhimurium infection; the failure to confer full resistance could be explained by the absence of several functional capabilities identified by metagenome analyses.

Functional genomic analysis of the Oligo-MM¹² consortium was performed, and by comparing it to that of a conventional microbiome, researchers identified its missing functions. The researchers created an improved version of the Oligo-MM¹² bacterial community that harboured three facultative anaerobic bacteria (Escherichia coli Mt1B1, Streptococcus danieliae ERD01G and Staphylococcus xylosus 33-ERD13C) from the mouse intestinal bacterial collection (miBC); this new version indeed provided conventional-like CR. Facultative anaerobic bacteria, especially E. coli Mt1B1, had an important role in promoting CR against S. Typhimurium by mechanisms that included competition for oxygen or anaerobic electron acceptors such as nitrate.

In conclusion, these researchers developed a model microbiota that can be used for enhancing CR; they also demonstrated how microbial communities can be designed using a genome-guided approach, which can serve as a basis for exploring additional strains in the context of enteric infections.

Reference:

Brugiroux S, Beutler M, Pfann C, et al. Genome-guided design of a defined mouse microbiota that confers colonization resistance against Salmonella enterica serovar Typhimurium. Nat Microbiol. 2016; 2:16215. doi: 10.1038/nmicrobiol.2016.215.