The sixth sense of the brain: interoception in organoid study.

Interoception is the process by which the nervous system senses, integrates, and interprets signals arising from within the body, thereby enabling the brain to monitor and regulate physiological functions. Often described as a "sixth sense", interoception links internal physiological states to brain-mediated homeostatic control, whereas sight, smell, hearing, taste, and touch primarily convey information from the external environment. Organoids are three-dimensional tissue models derived from stem or progenitor cells that reproduce selected structural and functional features of native organs. Because organoids are increasingly used in disease modeling, drug testing, and regenerative research, their integration with neural, endocrine, immune, and vascular components offers an opportunity to investigate brain-body communication. Conversely, organoid-based systems may provide experimentally tractable models for interoception. This review defines interoception and organoid technologies, examines brain-centered communication with skeletal and intestinal systems, and discusses how brain, bone, and intestinal organoids and assembloids could advance interoception research. In particular, organoid-based models may enable mechanistic investigation of neuroendocrine pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, and thereby provide new insights into physiological regulation and disease progression.