The study by Wikoff et al. investigates the impact of gut microflora on mammalian blood metabolites using mass spectrometry-based metabolomics. The researchers compared plasma extracts from germ-free mice (GF) with those from conventional (conv) animals, finding that the gut microbiome significantly affects the composition of blood metabolites. Hundreds of features were detected in only one sample set, with most being unique to the conv animals, while about 10% of all features showed significant changes in relative signal intensity between the two groups. Amino acid metabolites were particularly affected, with bacterial-mediated production of bioactive indole-containing metabolites like indoxyl sulfate and indole-3-propionic acid (IPA) being impacted. The production of IPA was found to be dependent on gut microflora and could be established by colonization with *Clostridium sporogenes*. The study also observed a broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome, suggesting that the gut microflora directly impacts the host's drug metabolism capacity. These findings highlight a significant interplay between bacterial and mammalian metabolism.The study by Wikoff et al. investigates the impact of gut microflora on mammalian blood metabolites using mass spectrometry-based metabolomics. The researchers compared plasma extracts from germ-free mice (GF) with those from conventional (conv) animals, finding that the gut microbiome significantly affects the composition of blood metabolites. Hundreds of features were detected in only one sample set, with most being unique to the conv animals, while about 10% of all features showed significant changes in relative signal intensity between the two groups. Amino acid metabolites were particularly affected, with bacterial-mediated production of bioactive indole-containing metabolites like indoxyl sulfate and indole-3-propionic acid (IPA) being impacted. The production of IPA was found to be dependent on gut microflora and could be established by colonization with *Clostridium sporogenes*. The study also observed a broad, drug-like phase II metabolic response of the host to metabolites generated by the microbiome, suggesting that the gut microflora directly impacts the host's drug metabolism capacity. These findings highlight a significant interplay between bacterial and mammalian metabolism.