A mosaic of cross-phyla chemical interactions occurs between all metazoans and their microbiomes. In humans, the gut harbors the heaviest microbial load, but many organs, particularly those with a mucosal surface, associate with highly adapted and evolved microbial consortia. The microbial residents within these organ systems are increasingly well characterized, yielding a good understanding of human microbiome composition. However, we have yet to elucidate the full chemical impact the microbiome exerts on an animal and the breadth of the chemical diversity it contributes. A number of molecular families are known to be shaped by the microbiome including short-chain fatty acids, indoles, aromatic amino acid metabolites, complex polysaccharides, and host sphingolipids and bile acids. These metabolites profoundly affect host physiology and are being explored for their roles in both health and disease. The synthesis of bile acids takes place in the liver and recent research has shown that bile acids can act as signaling molecules and activate a number of molecules. A primary focus has been on the Farnesoid X receptor (FXR) which plays an important role in bile acid synthesis and in regulation of glucose, lipid and energy metabolism.