Lifestyle-related diseases, an aging society, and the recent pandemic of a novel coronavirus infection are becoming serious and urgent social problems far beyond our imagination. In our strategic efforts to eliminate or minimize these problems, the role of functional foods as “life-saving foods," which are supposed to contribute to the maintenance and improvement of health, is extremely important. In this paper, to contribute to the efficient development and marketing of functional foods that are truly effective in humans, various dynamics of food components in the small and large intestines, which are fundamentally different in function and environment, and the differences between the intestinal environments of experimental animals and humans are outlined. Subsequently, “human intestinal models" developed by the authors on the above basis and examples of their use are presented. In addition, some improvements need to be made to implement such models in society as trusted tools for evaluating the functionality of food ingredients before human intervention studies are addressed.

The gut microbiota is a complex ecosystem composed of microorganisms in the digestive tract, and it is involved in maintaining our health and the development of various diseases. Behind the proliferation of studies of the gut microbiota are important technologies for understanding the function of gut bacteria, such as metagenomic analysis by next-generation sequencers or gnotobiotic animal models. However, the detailed molecular mechanism of the interaction between host cells and intestinal bacteria remains unknown due to the lack of an in vitro co-culturing system. Although co-culturing host cells together with gut bacteria has been considered difficult because they have different oxygen demand characteristics, interdisciplinary research, covering organoids (stem cell biology), microfluidic devices (engineering), and microbiology have enabled the generation of novel organoid-culturing systems of human host cells with anaerobic gut bacteria. Therefore, expectations are high that these co-culturing systems will be used in the future to reveal the molecular basis of the symbiotic relationships between host and micro-organisms.