Reproducible Colonization of Germ-Free Mice With the Oligo-Mouse-Microbiota in Different Animal Facilities

Abstract

The Oligo-Mouse-Microbiota (OMM¹²) is a recently developed synthetic bacterial community for functional microbiome research in mouse models (Brugiroux et al., 2016). To date, the OMM¹² model has been established in several germ-free mouse facilities world-wide and is employed to address a growing variety of research questions related to infection biology, mucosal immunology, microbial ecology and host-microbiome metabolic cross-talk. The OMM¹² consists of 12 sequenced and publically available strains isolated from mice, representing five bacterial phyla that are naturally abundant in the murine gastrointestinal tract (Lagkouvardos et al., 2016). Under germ-free conditions, the OMM¹² colonizes mice stably over multiple generations. Here, we investigated whether stably colonized OMM¹² mouse lines could be reproducibly established in different animal facilities. Germ-free C57Bl/6J mice were inoculated with a frozen mixture of the OMM¹² strains. Within 2 weeks after application, the OMM¹² community reached the same stable composition in all facilities, as determined by fecal microbiome analysis. We show that a second application of the OMM¹² strains after 72 h leads to a more stable community composition than a single application. The availability of such protocols for reliable de novo generation of gnotobiotic rodents will certainly contribute to increasing experimental reproducibility in biomedical research.

Keywords: 3R; Oligo-MM12; defined bacterial consortia; gnotobiology; isobiotic mice; minimal microbiome; sDMDMm2; syncom.