Microfluidic Gut-on-a-Chip Models for Functional Food Evaluation: From Digestion Kinetics to Personalized Nutrition

The accurate assessment of the gastrointestinal fate of functional food ingredients is critical for substantiating health benefits. However, conventional in vitro models do not fully capture the dynamic, multicellular, and physicochemical environment of the human intestine, creating a predictive gap. Microfluidic gut-on-a-chip (GOC) technology provides a microphysiological approach by integrating fluid flow, mechanical cues, and multicellular co-cultures into a controllable biomimetic platform. This review critically examines the potential applications of GOC systems in evaluating food bioactives. We first summarize core design principles, including biomimetic architecture, material selection, mechanical stimulation, shear stress, and oxygen or chemical gradient control. We then discuss their applications in sequential digestion, intestinal absorption, barrier assessment, host-microbiota interactions, disease-specific modeling, and personalized nutrition. We provide a balanced analysis of the advantages and limitations of GOC systems, with emphasis on physiological relevance in selected contexts, real-time monitoring, material-related analytical bias, biological variability, throughput, standardization, regulatory acceptance, and industrial scalability. Finally, we discuss three application-oriented pathways for food-industry translation: high-throughput screening platforms, personalized formulation testing, and multi-organ microphysiological systems for systemic efficacy and safety assessment. As the field matures, GOC technology may serve as a supportive tool for evidence-based functional food development by bridging conventional in vitro assays and human intervention studies.