PSI-5 - Potential involvement of ferroptosis in lipopolysaccharide-induced intestinal inflammation in broilers

Abstract: Ferroptosis is a recently discovered form of programmed cell death that is characterized by iron-dependent lipid peroxidation. Several studies have indicated that ferroptosis might involve in various intestinal disease, including intestinal ischemia/reperfusion injury, Crohn’s disease and ulcerative colitis. In poultry, inflammatory bowel diseases (IBDs) resulting from pathogen invasion, nutritional deficiencies or environmental factors, might significantly reduce productivity and feed conversion rates of broilers, leading to economic losses for the industry. However, it is unclear whether ferroptosis contributes to the development of IBDs in broilers. In present study, we aimed to investigate the potential involvement of ferroptosis in the development of intestinal inflammation in broilers. A total of 192 one-day-old Ross308 broilers were randomly divided into four treatments, with 4 pens per treatment and 12 birds per pen. The treatments consisted of intraperitoneal injections of 0.9% sterile saline as control (CON) and 0.5, 1.0, 5.0mg/kg LPS, respectively (LL, ML, HL). The results showed that the administration of LPS decreased body weight of broilers compared to CON group at 21d of age (P < 0.05). Additionally, at 1-21d of age, the average daily gain of broilers was significantly decreased relative to CON group (P < 0.05). Histological examination revealed that treatment with LPS decreased the villi lengths while increased the crypt depths of ileum in HL group compared to CON group (P < 0.05). Furthermore, the relative mRNA expression of lipid peroxidation and iron accumulation-associated genes were significantly increased in jejunum and ileum in HL group (P < 0.05). Importantly, the untargeted metabolomics analysis of serum samples showed that cysteine and methionine metabolism was the most significant pathway differences between HL and CON groups, indicating that the key antioxidant in ferroptosis mechanism, glutathione, might be affected after the administration of LPS. The results suggested that ferroptosis might involve in lipopolysaccharide-induced intestinal inflammation in broilers. Further investigations are required to elucidate the underlying mechanisms of how ferroptosis contributes to inflammatory bowel disease in broilers.