Dietary Copper Improves Intestinal Morphology via Modulating Intestinal Stem Cell Activity in Pigs

SIMPLE SUMMARY: Copper (Cu) is one of the essential trace elements for animal growth. Piglet intestinal epithelium undergoes a complete renewal driven by intestinal stem cells located at the crypt base. However, whether Cu improves intestinal morphology and development via modulating intestinal stem cell activity in pigs remains unclear. This study aimed to investigate the effects of dietary Cu during the weaning period on the intestinal morphology and development of weaned and finished pigs and explored the potential mechanism by culturing the intestinal organoids and treated them with Cu in vitro. The results indicated that Cu supplementation during the weaning period improves the intestinal morphology in finishing pigs by modulating the activity of intestinal stem cells. ABSTRACT: Copper (Cu) is an essential micronutrient for animals. Many studies have been conducted on the effects of dietary Cu on growth performance, intestinal morphology, and function of piglets. However, the underlying mechanism remains to be explored. Intestinal stem cells (ISC) drive the development and constant renewal of intestinal epithelium. Therefore, we hypothesized that dietary Cu affects piglets’ intestinal development via modulating ISC activity. A total of eighty-five 21-day-old piglets were randomly assigned to five groups, where 25, 50, 75, 100, and 125 mg CuSO(4)/kg on a dry matter basis were supplemented to the basal diet at phase 1 (day 0 to 21). Increasing the dietary Cu concentration decreased (p < 0.05) villus width but increased (p < 0.001) the number of Ki67-positive cells. At phase 2 (day 22 to 163), the other 45 pigs were offered the same diets. Villus height in the 125 mg/kg Cu group was greater (p < 0.001) than in the other groups. Moreover, the effects of Cu on ISC activity in vitro were tested to explore the underlying mechanism. Compared to the control group, 10 μmol/L CuSO(4)·5H(2)O increased (p < 0.001) the organoid budding efficiency, crypt depth, and crypts per organoid. Dietary Cu improved the intestinal morphology of finishing pigs via promoting cell proliferation and modulating ISC activity.