Involvement of ferroptosis in lipopolysaccharide-induced intestinal inflammation in broilers

This study aimed to investigate whether lipopolysaccharide (LPS)-induced intestinal inflammation involves ferroptosis and its impact on broiler gut health. Two animal trials were conducted. In the first trial, 192 ROSS 308 broilers were randomly assigned to four groups and intraperitoneally injected with either 0.9 % sterile saline (control) or different doses of LPS (0.5, 1.0, and 5.0 mg/kg body weight) on days 16, 18, and 20. The results suggested that ferroptosis-related changes might occur in the intestine at the 5.0 mg/kg LPS dose, but the effects were not significant. Thus, a second trial was conducted with a shorter observation period. In this trial, 42 broilers were administered 5.0 mg/kg LPS or saline and sampled at 4, 8, and 24 h after the final injection to analyze ferroptosis-related markers in the intestine. Results showed that high-dose LPS significantly affected broiler growth performance, reducing average daily gain (ADG) and increasing feed conversion ratio (FCR). Intestinal morphology analysis revealed a decrease in villus height and an increase in crypt depth in the LPS-treated group, indicating intestinal structural damage. Quantitative PCR (qPCR) analysis demonstrated significant alterations in the expression of ferroptosis-related genes (e.g., FTH1, NCOA4, GPX4, ACSL4) in the intestinal tissue following LPS treatment. Additionally, LPS administration elevated total iron and ferrous iron levels in the intestine, further supporting the involvement of ferroptosis in inflammation. Metabolomic analysis indicated significant changes in specific intestinal metabolites associated with ferroptosis and inflammatory responses. In conclusion, this study confirms that LPS induces intestinal inflammation in broilers and may exacerbate damage through ferroptosis, providing valuable insights for developing nutritional strategies to improve broiler gut health.