Our understanding of how differences in microbiome traits influence host physiology, and ultimately, health outcomes, remains in its relative infancy. In part, this is due to the sheer complexity of microbiome-host interactions and the number of different potential points of direct or indirect interaction between the gut microbes and the host. Analysis of the functional capacity of the microbiome (based on bacterial pathways encoded by the metagenome), enabled us to identify differences in functional capacity between study populations. However, functional redundancy within the gut microbiome, as well as widespread cross-metabolism, makes predicting the impact of such differences in overall microbiome output extremely difficult. We suggest that analysis of the gut metabolome could provide important insight into the nature of host-microbiome interactions. Furthermore, in addition to assessment of inflammatory cytokines, other factors that potentially contribute to diet-microbe-host interactions, such as plasma metabolites, warrant investigation.