The OMM¹² mice: a decade of dissecting host-microbiome interactions

Humans and their associated microbes form a multifaceted ecosystem. Gaining mechanistic insight into this system necessitates reductionist models integrating ecological and immunological dimensions. Over the past decade, the gnotobiotic Oligo-Mouse-Microbiota (OMM¹²) mouse line has exemplified this approach, pairing a standardized consortium of 12 bacterial strains representative of the five major phyla of the mouse microbiota, with the most widely used host background, C57bl/6 mice, in microbiome research. Across numerous studies, this reproducible and experimentally tractable model has enabled the identification of molecular mechanisms underlying colonization resistance, pathogen virulence, microbiota-dependent metabolic and immune pathways, as well as bacterial and bacteriophage dynamics. The modular ability/nature of the OMM¹² model may now be further leveraged and refined in different host and microbial dimensions to address remaining gaps in translational microbiome research, positioning it as a reference framework for mechanistic investigations.