In vitro digestion models in food chemistry: advancements, challenges, and applications in nutrient bioaccessibility and bioavailability

Modern food chemistry and nutrition research stresses digestion and bioavailability. In vitro digestive models are needed to reconstruct the human gastrointestinal (GI) system and study food-derived chemical release, transformation, and absorption. This review examines major in vitro digestion platforms, including static and dynamic systems, organ-on-chip devices, and 3D-bioprinted gut models. Integrating these models with absorption simulators such as Caco-2 cells and advanced analytical instruments (e.g., HPLC, LC-MS/MS, FTIR, NMR, and OMICS technologies) enables comprehensive profiling of digestion products. These models assess bioaccessibility and bioavailability of polyphenols, omega-3 fatty acids, and encapsulated nutraceuticals. Computer modeling and artificial intelligence (AI) increase prediction for high-throughput functional food performance screening. Though promising, current models lack homogeneity and microbial representation often does not fully replicate in vivo gut microbiota complexity. In vitro digestive models assist food scientists enhance products. Priorities include harmonizing INFOGEST protocols, improving physiological relevance, and customizing nutrition and clinical validation. These developments may strengthen the utility of in vitro models in precision nutrition and industrial applications. • Review of key static and dynamic in vitro digestion models. • Comparison of model accuracy in mimicking GI conditions. • OMICs tools boost understanding of digestion mechanisms. • Analytical methods track nutrient release and changes. • Advances in gut-on-chip and 3D models for relevance.