Mediation is not the only way in which the microbiome can influence how dietary, lifestyle, and environmental factors influence pathophysiology. The microbiome can also interact with these relationships in such a way that the association of dietary, lifestyle, and environmental factors with pathophysiology depends on the presence/absence of a particular microorganism. Given that systolic blood pressure is an important chronic disease risk factor, and was higher in Mer than in Waiben systolic blood pressure was selected for an analysis of interaction. A microbiome-wide interaction study was performed, and, after correcting for multiple comparisons, Alistipes onderdonkii (NCBI:txid328813) was identified as a microorganism that significantly interacted with the island-systolic blood pressure relationship (Figure 5). The pattern of interaction was such that a failure to detect Alistipes onderdonkii in the gut microbiome was associated with increased systolic blood pressure, but only in Mer, and when these microorganisms were present, systolic blood pressure in Mer was identical to that of Waiben residents. These effect modifications remained even after adjusting for various diet and lifestyle exposure variables, suggesting that higher systolic blood pressure in Mer residents, despite Mer residents having lower traditional exposure risk factors, may be explained by an interaction between geographic location and the gut microbiome.