Metabolism by ex vivo cultures of human stool increases the activity of coumarin, a widespread antioxidant from herbal supplements

Host and microbiome metabolism of bioactive compounds can alter their efficacy. Herbal supplements contain many bioactive compounds, but their metabolism by gut microbes and the effects on efficacy remain poorly understood. To gain clarity, we investigate coumarin, an antioxidant in food, cosmetics, and supplements and a scaffold for diverse bioactive compounds. In this study, we characterize coumarin metabolism by the human gut microbiome, which produces 3,4-dihydrocoumarin and melilotic acid. We characterize this pathway in the culturable microbiota from 9 stool donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomics and microbiome profiling. We discover that 17 microbiome species metabolize coumarin and that the E. coli gene nemA is necessary for coumarin reduction. In antioxidant assays, melilotic acid is more potent than coumarin, suggesting that this pathway may impact bioactivity, with possible contributions to supplement efficacy. Further characterization may provide insights on the metabolic fate of coumarins and contributions of the microbiome to their efficacy.