Despite the recognized importance of the human microbiome, it is not yet clear how humans acquire their associated microbes, nor is it understood what underlies variation in microbiomes across individuals. It is also not clear how the microbiome interacts with the human genome and the external environment to determine human phenotypes. The microbiome has often been referred to as a “second genome” (e.g., Grice & Segre 2012), and as such, one could think of microbiome influences on phenotypes as a type of “genetic” effect (the G in G × E). However, this is not completely true; the microbiome of an individual is more variable and more dynamic than an individual’s genome, and its composition is more sensitive to the surrounding environment than that of the genome (e.g., Franzosa et al., 2015). In this sense, the microbiome can be thought of as part of the “environment” (the E in G × E).
