PSIX-20 Nrf2 Pathway Mediates Resistance to Weaning Stress-Induced Intestinal Injury in Piglets of Different Breeds

The intestine is the central organ of early weaning stress in piglets; however, the response of intestinal stem cells (ISCs) that drive epithelial renewal between the different breeds of piglets is not yet known. Therefore, this investigation was to explore the sensitivity of ISCs to early weaning stress. Taoyuan Black and Duroc piglets were slaughtered at 21 days of age (on the day of weaning) and 24 days of age (3 days after weaning) with 10 pigs, respectively. And the results showed that Taoyuan Black pigs are more tolerant to early weaning stress, while the mucosal mass of jejunum was significantly decreased in 24-day-old Duroc piglets compared with the 21-day-old Duroc piglets (P < 0.05). The weaning stress damaged the jejunal structure, decreased the expression of tight junction related proteins ZO-1, Occludin, and Claudin-1, and increased intestinal permeability in Duroc piglets (P < 0.05). The ex vivo intestinal organoids (IOs) derived from the jejunal crypt of Duroc piglets after weaning exhibited lower expansion efficiency (P < 0.05). Furthermore, the levels of proliferating cell marker PCNA, terminally differentiated cell marker KRT20, absorptive cell marker Villin, goblet cell marker MUC2, and Paneth cell marker lysozyme were significantly reduced in the jejunum, crypt, and jejunal organoids of 24-day-old Duroc (P < 0.05). ROS levels in the jejunum of Duroc piglets were increased along with the inhibition of the Nrf2 pathway compared with 21-day-old Duroc piglets (P < 0.05). Collectively, the Taoyuan Black pigs had stronger tolerance to weaning stress; however early weaning suppressed the Nrf2 pathway, decreased proliferation and differentiation activity of ISCs, and disrupted intestinal homeostasis in Duroc piglets.