Metabolomic analysis of intestinal epithelial cell maturation along the crypt–villus axis

Epithelial cells along the crypt–villus axis (CVA) undergo continual renewal through highly coordinated proliferation, differentiation, and apoptosis; however, the changes in metabolism during maturation along the CVA are still unclear. The present study investigates the global metabolite changes in intestinal epithelial cells during maturation along the CVA. Eight 21 day-old suckling piglets were used. Intestinal epithelial cells were isolated sequentially from the villus top to the bottom of the crypt with 6 fractions (F1 to F6), and GC-MS was used to identify the metabolites, whose levels changed. Three hundred metabolites were identified. PLS-DA and OPLS-DA analyses showed that the metabolism of intestinal epithelial cells gradually changed during maturation along the CVA. These analyses were also run to distinguish between two fractions of cells, and yielded good separation of F1 and F3, F1 and F4, F1 and F5, and F1 and F6 cells. Significant differences were found in the metabolism of fatty acids, amino acids, glucose, and other metabolites between villus cells and crypt cells. These results reveal a global change in cellular metabolism during maturation along the CVA, and provide basal information for understanding the mechanism involved for specific nutrients in regulating epithelial cell renewal and identifying nutrients to regulate mucosal morphology and functions.