The composition of the microbiota of all metazoans plays an important role in host physiology, with microbe-derived natural products acting as the chemical messengers interacting with host systems. To examine the global impact of the microbiome on chemical composition, Quinn et al. performed metabolomics analyses across 96 sample sites, representing 29 different organs in both germ-free (GF) and colonized (SPF) mice, and found that the microbiome affects the chemical make-up and metabolic transformations in all organs, including organs that are very distant from the gastrointestinal (GI) tract. The most molecularly diverse region was the colon of SPF mice. An analysis of chemical transformations in metabolites in the lower GI tract showed that the microbiota contributed more to catabolic breakdown than to anabolism. However, among the signals associated with SPF mice that did contribute to anabolism were three unique amino acid amide conjugates of cholic acid that correlated with the presence of Clostridium sp. Two of these could agonize a key human bile acid receptor, FXR, and were also found, using data from public metabolomics repositories, to be linked to diet in animals and human gut dysbiosis and disease. These findings aid in understanding the connections between the microbiota, metabolites, and host health.