Vitamin K protects against lipopolysaccharide-induced intestinal inflammation in piglets by inhibiting the MAPK and PI3K-AKT pathways.

Background: The benefits of Vitamin K (VK) in mitigating inflammation have been well-established, while the underlying mechanisms remain not yet fully elucidated. This study aimed to investigate its protective effects and underlying mechanisms in LPS-induced intestinal inflammation of piglets. Methods: In a 21-day study, 24 weaned piglets were randomly assigned to 4 groups: CON group (basal diet), VK group (basal diet + 4.5 mg/kg VK3), LPS group (basal diet + LPS challenge), LPS+VK (basal diet + 4.5 mg/kg VK3 + LPS challenge). On day 21, LPS or saline was administered to the piglets by intraperitoneal injection. The IPEC-J2 cells were treated with or without VK and LPS for 24 h and analyzed with various assays. Results: Morphological analysis revealed that VK significantly restored the decreased villus height and ratio of villus height to crypt depth induced by LPS. VK effectively upregulated tight junction proteins claudin-1 expression. Furthermore, VK notably suppressed the overexpression of TNF-α, IL-1β, IL-6, and IL-8, as well as the concentrations of diamine oxidase (DAO) and reactive oxygen (ROS), while restoring the reduced expression of Conclusion: These results indicated that VK alleviated intestinal inflammation in piglets by inhibiting the MAPK and PI3K-AKT signaling pathways as well as the regulation of in the gut microbiota.