Crosstalk Within the Intestinal Epithelium: Aspects of Intestinal Absorption, Homeostasis, and Immunity

Gut health is crucial in many ways, such as in improving human health in general and enhancing production in agricultural animals. To maximize the effect of a healthy gastrointestinal tract (GIT), an understanding of the regulation of intestinal functions is needed. Proper intestinal functions depend on the activity, composition, and behavior of intestinal epithelial cells (IECs). There are various types of IECs, including enterocytes, Paneth cells, enteroendocrine cells (EECs), goblet cells, tuft cells, M cells, and intestinal epithelial stem cells (IESCs), each with unique 3D structures and IEC distributions. Although the communication between IECs and other cell types, such as immune cells and neurons, has been intensively reviewed, communication between different IECs has rarely been addressed. The present paper overviews the networks among IECs that influence intestinal functions. Intestinal absorption is regulated by incretins derived from EECs that induce nutrient transporter activity in enterocytes. EECs, Paneth cells, tuft cells, and enterocytes release signals to activate Notch signaling, which modulates IESC activity and intestinal homeostasis, including proliferation and differentiation. Intestinal immunity can be altered via EECs, goblet cells, tuft cells, and cytokines derived from IECs. Finally, tools for investigating IEC communication have been discussed, including the novel 3D intestinal cell model utilizing enteroids that can be considered a powerful tool for IEC communication research. Overall, the importance of IEC communication, especially EECs and Paneth cells, which cover most intestinal functional regulating pathways, are overviewed in this paper. Such a compilation will be helpful in developing strategies for maintaining gut health.