Novel functions of taste-like cells: Organoid-reconstructed sensory interfaces

Endoderm-derived organs, including the gastrointestinal tract, play central roles in nutrient digestion and absorption. They simultaneously function as an "internalized external environment" that continuously interfaces with exogenous substances, thereby constituting a frontline of host defense. Chemosensory cells within the gastrointestinal epithelium, such as enteroendocrine cells and tuft cells, use molecular mechanisms analogous to those of taste reception to detect nutrients and xenobiotic compounds. However, because these populations are sparse, a comprehensive understanding of their functions is limited.

Organoid culture systems have been developed to investigate rare chemosensory cells in endoderm-derived organs, including the gastrointestinal tract, pancreas, and taste buds, with studies progressing from mouse to primate models to improve translational relevance. Here, recent findings using primate-derived organoids of the gastrointestinal tract, pancreatic ducts, and taste buds are introduced, with particular emphasis on tuft cells.

A working hypothesis is proposed in which sustained low-level chemical stimulation of tuft cells helps maintain the host defense system in a primed state, a state termed "immune idling," and this framework is discussed in relation to the possible biological significance of human bitter preference. Thus, endodermal chemosensory mechanisms may function as an integrated system linking metabolic regulation and host defense.