Chicken enteroid kinome responses to Salmonella infection and organic acid/essential oil blend

     

Enteroids provide a 3-dimensional microenvironment of the intestine, acting as a miniature model for understanding intestinal functions and immune responses. Hence, this shows a promising application in studying disease models and drug screening, among others. Salmonella enterica serovar Typhimurium is one of the food-borne pathogens affecting human health through production animals due to contaminated meat consumption. Research focus on discovering new antibiotic alternatives has increased to minimize the use of antibiotics in production animals, ostensibly preventing the development of antibiotic resistance in farm animals, humans, and pathogens. One of these antibiotic alternatives is a blend of organic acids and essential oils. Here, we use the enteroid model to understand host responses and disease pathogenesis toward Salmonella enterica infection and the antibiotic alternative from an immunometabolic perspective using the species-specific kinome array technique. The experimental groups include enteroids alone, + Salmonella, + 0.25 mg/mL product, + 0.5 mg/mL product, + 0.25 mg/mL product and Salmonella, and 0.5 mg/mL product and Salmonella. We performed statistical data analysis on the kinome array data and finalized 4 significant signal transduction pathways using a P-value and a false discovery rate of < 0.05. These are insulin signaling pathway, T cell receptor pathway, PI3K-AKT signaling pathway, and FoxO signaling pathway. Results show an inclusion rate of 0.5 mg/mL of product, and the Salmonella inoculation results in an immune stimulatory response. The inclusion rate of 0.5 mg/mL with Salmonella and 0.25 mg/mL with and without Salmonella results in a balanced effector response downstream of the PI3K-Akt pathway. Our future work includes analyzing significant fold changes occurring in peptides of the respective signal transduction pathway and their relevance to the effect on the enteroids and the Salmonella-infected enteroids. This work will help us understand the ability of the enteroids to act as an alternative model of the chicken gut, providing a rapid way to screen antibiotic alternatives and their compatibility through the host responses against them.

Key Words: Salmonella, immunometabolism, enteroids.