Using the natural variation of mouse populations to understand host-gut microbiome interactions

One approach to understanding gut microbiome–host interactions, described in this review, is to examine how natural variation in a model organism, where environmental factors can be controlled, affects the microbiome and, in turn, how the microbiome is associated with physiological or clinical traits. A variation of this approach, termed “systems genetics” is to characterize both the microbiome and the host using various high throughput technologies, such as metabolomics or gene expression of the microbiome and the host. By relating variation in the microbiome and host functions to such “molecular phenotypes”, hypotheses can be generated and then experimentally tested. To model human gut microbiome–host interactions in this way, the mouse is particularly useful given the extensive body of genetic resources and experimental tools that are available.