Exploring the protective mechanism of exogenous melatonin on intestine of heat-stressed chicks based on network pharmacology and intestinal microbiota analysis

Abstract

Heat stress constitutes a severe risk to the health of poultry, not only damaging intestinal health, but also reducing antioxidant defenses and weakening the immune response. Exogenous melatonin can enhance the antioxidant capacity of heat-stressed chicks through the cecal microbiota, and reduce the inflammatory response and intestinal barrier damage. 21-day-old Hy-Line brown chicks were divided into control group, heat stress group, and three groups receiving different doses of melatonin (0.5, 1.0, 2.0 mg/kg). Except for the control group (22 ± 2 °C from 00:00 to 24:00 daily), all other groups were exposed to a high-temperature environment (34 ± 2 °C, from 08:00 to 18:00 daily) for 21 consecutive days. The results showed that heat stress significantly decreased final body weight of chicks, increased serum MDA, IL-1β, IL-6, TNF-α, D-LA and DAO levels, decreased GSH-Px, CAT and SOD activities, and decreased jejunal and ileal villus height/crypt depth (VH/CD), cecal Firmicutes/Bacteroidetes (F/B) ratio and Lactobacillus abundance. Exogenous melatonin reversed these changes, and 1.0 mg/kg was the most effective. It included the recovery of antioxidant enzyme activity, the decrease of serum inflammatory factors, D-LA and DAO, the up-regulation of VH/CD and tight junction genes (CLDN1, OCLN, TJP1, MUC2) in jejunum and ileum, the increase of cecal F/B ratio and the enrichment of Lactobacillus. Network pharmacology and molecular docking identified the core targets of anti-oxidation and anti-inflammation. Melatonin reduced heat stress-induced intestinal injury by reducing inflammation and oxidative stress.