Advances in data collection (high throughput shotgun metagenomics, transcriptomics, and metabolomics) and analysis (bioinformatics and multiomics) led to the realization that all mammals are metaorganisms, shaped not only by their own genome but also by the genomes of the microbes that colonize them. To date, most studies have focused on the bacterial microbiome, whereas curated databases for viruses, fungi, and protozoa are still evolving. Studies on the interdependency of microbial kingdoms and their combined effects on host physiology are just starting. Although it is clear that past and present exposure to commensals and pathogens profoundly affect human physiology, such exposure is lacking in standard preclinical models such as laboratory mice. Laboratory mouse colonies are repeatedly rederived in germ free status and subjected to restrictive, pathogen free housing conditions. This review summarizes efforts to bring the wild microbiome into the laboratory setting to improve preclinical models and their translational research value.