Fermentation-Derived Phenolic Compounds: Mechanisms of Release, Bioavailability, and Functional Health Benefits

Phenolic compounds underpin many health benefits of plant-based diets yet often exhibit poor bioavailability due to glycosylation, esterification, polymerization, and matrix entrapment. This review synthesizes mechanistic and translational evidence that microbial fermentation can act as a natural bioactivation platform for phenolics. Using a structured search, we included studies on plant phenolics undergoing microbial or enzyme-assisted fermentation that reported quantitative phenolic outcomes, bioaccessibility, or pharmacokinetic (PK) endpoints, and excluded purely chemical hydrolysis unless used as a comparator. Evidence was graded across chemistry, in-vitro digestion, animal, and human tiers, with extraction of substrate, microbes/enzymes, conditions, analytes, assays, and outcomes. Across diverse matrices, fermentation drives deglycosylation, de-esterification, depolymerization, and acyl/acetylation, increasing solubility and oxidative stability while softening plant cell-wall barriers to improve bioaccessibility. In the colon, liberated precursors are converted to urolithins, enterolignans, and phenyl-γ-valerolactones, which are generally more bioavailable and mechanistically aligned with vascular, metabolic, and anti-inflammatory effects than their precursors. Human PK data indicate aglycone-enriched foods frequently show higher C-max/AUC and earlier T-max than glycoside-rich counterparts, while validated exposure biomarkers capture colonic metabolism with substantial inter-individual variability driven by microbiome metabotypes. Collectively, the evidence positions fermentation as a scalable route to design phenolic-rich foods and ingredients with predictable bioavailability and function.