How Gut Microbes Transform Dietary Phytonutrients: Enzymatic Pathways and Human Metabolite Exposure

Compounds identified in plant foods are often not the species that reach human tissues. Glycosides, tannins and incompletely absorbed aglycones enter the colon, where gut microorganisms hydrolyse, reduce, cleave, demethylate or dehydroxylate them. This critical narrative review examines pathways resolved beyond taxonomic association: daidzein-to-S-equol conversion; cooperative urolithin and enterolignan formation; flavone reduction and C-ring cleavage; stereoselective catechin metabolism; glucosinolate activation; and transformations of resveratrol and hydroxycinnamate-derived metabolites. We distinguish enzyme and genetic evidence from findings in isolates, consortia, faecal communities, gnotobiotic models and human studies. Detecting a taxon or catalytic gene does not establish in vivo pathway flux. Substrate release, transcription, cofactor supply, cross-feeding, product consumption, absorption and host conjugation shape the metabolites detected in plasma and urine. Human studies identify distinct S-equol and urolithin phenotypes and show substantial exposure to phenyl-γ-valerolactones and smaller phenolic acids, although several high-flux reactions remain enzymatically unresolved. Biological relevance is most credible when tested with circulating conjugates at concentrations attained after food intake. Linking reaction-level microbiology to measured exposure may explain interindividual responses to phytonutrient-rich foods. We conclude that microbiota-dependent exposure should be claimed only when reaction-level evidence is connected to precursor-specific human metabolites. This framework separates established conversion from unresolved spontaneous and host processing and specifies the evidence needed to explain individual responses.