Gut Microbiota-Mediated Biotransformation of Coumarins.

1. Coumarins are plant-derived secondary metabolites widely present in foods, spices, and medicinal plants. Their limited intestinal absorption and extensive host metabolism allow a variable fraction to reach the colon, where gut microorganisms can transform them into metabolites with distinct physicochemical and biological properties.2. This review synthesizes current evidence on gut microbiota-mediated coumarin biotransformation, focusing on microbial taxa, metabolic reactions, structural determinants, and consequences for biological activity. Reported transformations include deglycosylation, reduction, O-demethylation, hydroxylation, deprenylation, and lactone ring opening. Recent studies have identified multiple human gut bacteria capable of coumarin reduction and implicated the NADPH-dependent reductase NemA in this process. Gut bacteria may also generate simple coumarins from dietary phenolic precursors. These transformations can modify biological activity, while coumarins and their metabolites may reciprocally influence microbial composition and metabolism.3. Current evidence supports gut microbiota as an important determinant of coumarin metabolism, but its physiological relevance in humans remains uncertain. Key gaps include interindividual variability, specific microbial enzymes and taxa, enterohepatic recycling, and the contribution of the gut mycobiome. Integrated microbiome, metabolomic, and pharmacokinetic approaches are needed to establish the contribution of microbiota-derived metabolites to coumarin bioactivity and safety.