Uridine inhibits the stemness of intestinal stem cells in 3D intestinal organoids and mice.

The activity of intestinal stem cells (ISCs) is foremost in maintaining homeostasis and repair of intestines. As a pivotal substrate of RNA and DNA biosynthesis, uridine plays essential roles in nutritional and disease monitoring. Whether uridine influences ISC activity remains undefined. To answer this question, 3-dimensional (3D) mouse intestinal organoids and living mice were used as a model. It was found that uridine causes a significant decrease in the number of crypts per intestinal organoid. Uridine also significantly decreases mRNA expression and protein levels with markers of ISCs in intestinal organoids in a dose-dependent manner, which was instructed via mTOR. In parallel, uridine decreases the expression of marker of ISCs in mouse intestine in vivo. Our findings are the first to demonstrate that uridine is able to govern the functions of ISCs in intestinal organoid and mouse models. Thus, this study may provide a useful reference for developing novel functional food bioactives that maintain intestinal homeostasis.

Enteroids: Promising in Vitro Models for Studies of Intestinal Physiology and Nutrition in Farm Animals.

The lack of sophisticated in vitro models limits our current understanding of gastrointestinal functions in farm animals. Conventional 2D cell lines or primary cells fail to recapitulate the physiology of in vivo intestinal epithelium. In contrast stem cell-derived, nontransformed 3D enteroids partially recreate the villus-crypt anatomy of the native intestine and comprise most if not all intestinal cell types including enterocytes, enteroendocrine cells, goblet cells, Paneth cells, and stem cells. This review summarizes the techniques used for generating and culturing enteroids of various farm animal species, focuses on important factors influencing the longevity of enteroids, and provides an overview of their current applications in modeling veterinary pathogens and in developing chemicals and bioactives for treating animal disease and improving production performance. It also mentions current limitations of enteroid models and potential solutions and highlights the opportunities for using these enteroids as a platform in studies regarding veterinary sciences and animal nutrition.