Selenomethionine alleviates LPS-induced PANoptosis in chicken cecum through the ROS/MAPK pathway, thereby mitigating inflammation and microbial dysbiosis.

Abstract

Selenomethionine (SeMet), a vital organic selenium compound, plays a pivotal role in maintaining redox homeostasis and is extensively utilized as a dietary supplement. The ROS/MAPK signaling axis has been implicated in mediating the detrimental effects of exogenous toxins on biological systems. However, the potential involvement of the ROS/MAPK signaling pathway in the protective mechanism of organic selenium against LPS-induced cecal injury in chickens remains to be elucidated. In this study, 80 Hailan brown laying hens aged 46 weeks were randomly allocated into four experimental groups (n = 20) to establish a model for evaluating the effects of dietary SeMet supplementation and/or LPS treatment. The experimental design comprised the following groups: the C group (basal diet), the SeMet -supplemented group (SeMet group), the LPS-treatment group (LPS group), and the combined SeMet and LPS treatment group (Se+LPS group). Results showed that SeMet mitigated LPS-induced cecal epithelial disruption, oxidative stress (ROS, HO, and MDA), and restored antioxidant enzyme activity. SeMet also suppressed MAPK signaling and PANoptosis-related protein expression (GSDMD, Caspase-3, MLKL), while enhancing intestinal tight junctions and reducing inflammation. Additionally, SeMet restored gut microbiota homeostasis. These findings demonstrate that SeMet alleviates LPS-triggered cecal PANoptosis by inhibiting the ROS/MAPK cascade, improving intestinal barrier function, and modulating microbial balance. Our findings provide novel insights into dietary SeMet as a potential nutritional strategy to mitigate cecal injury in poultry, with implications for improving gut health and productivity in commercial laying hens.