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

Huakai Wang^1*Ruiyu Ma¹Renrong Qi¹Zhen Liu¹Yinghao Li²Xudong Wu¹Chunfang Zhao²Qiugang Ma³Kai Zhan¹

• ¹Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Anhui Academy of Agricultural Sciences, Hefei, China
• ²Anhui Science and Technology University, Bengbu, China
• ³China Agricultural University, Beijing, China

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. 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. 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 and occludin 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 glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD). The combined analysis of transcriptome and proteome, as well as the Western blot verification, indicated that VK mainly mediates the restriction of the MAPK and PI3K-AKT signaling pathways. Moreover, VK relieved gut microbiota dysbiosis, such as decreasing in Spirochaetato. 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.