Quantitative Fate Mapping and Mass-Balance Analysis of Plant-Polyphenol Biotransformation during Simulated Gastrointestinal Digestion

In vitro digestion systems, ranging from static, one-compartment models to dynamic, multi-compartment models, are well-established platforms for evaluating the gastrointestinal bioaccessibility of polyphenolic plant compounds.  Digestion is considered a multistage biological process that includes hydrolysis, oxidation, deglycosylation, complexation with dietary macromolecules, and microbial catabolism. The composition of the plant matrix affects the release kinetics, physicochemical stability, and bioaccessibility of phytochemicals, resulting in a variety of low-molecular-weight metabolites. This systematic review examined 29 articles on advances in polyphenol quantitative fate mapping biotransformation during simulated gastrointestinal digestion and colonic fermentation.  A tailored database search strategy was applied across PubMed, ScienceDirect, and Scopus, focusing on medicinal plants rich in specific flavonoids and phenolic acids. Advanced analytical techniques and high-precision metabolomics are examined in the context of the structural annotation and quantitative determination of primary compounds, catabolic products, and gut microbiota-derived metabolites.  The results revealed that studies primarily focus on quantifying parent polyphenols before and after digestion with little data on digestive transformation pathways; consequently, the fate of many polyphenols remains unknown.  In vitro bioaccessibility studies should consider the chemical and biochemical reactions, as well as the physicochemical constraints, that occur within substrates. Key determinants of polyphenol bioaccessibility include matrix-dependent release kinetics, particle size distribution, partitioning dynamics, glycosylation status, and pH-dependent degradation pathways within the gastrointestinal tract. Overall, integrating LC-MS-based metabolomics profiling, transformation pathway reconstruction, and mass balance analysis clarifies digestive bioprocesses and leads to more reliable, quantitative results. This approach would overcome the limitations of existing bioavailability-based studies and encourage the development of next-generation nutraceutical ingredients designed to generate bioactive metabolites, rather than focusing on the initial phytochemical content. Furthermore, in vivo data validation is essential to consolidate process scalability.