Background: Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), severely affects patients’ quality of life. Sodium butyrate (NaB) has been reported to improve IBD manifestations, although its underlying mechanisms remain incompletely understood. Methods: An IBD mouse model was induced with 3% (w/v) dextran sulfate sodium (DSS). Mice were administered NaB (500 mg/kg, gavage), 5-aminosalicylic acid (5-ASA,150 mg/kg, gavage), or the ferroptosis inhibitor ferrostatin-1 (Fer-1, intraperitoneal injection). Western blotting (WB) and real-time quantitative PCR (RT-qPCR) were performed to evaluate ferroptosis-related molecules and target pathway components. Immunofluorescence staining was used to assess ferroptosis in macrophages preliminarily. Results: NaB alleviated clinical symptoms of IBD in mice, including mitigation of body weight loss, restoration of colon length, reduction in disease activity index (DAI), decreased spleen index, and protection of the intestinal barrier. In addition, compared with the DSS model group, NaB downregulated ACSL4 and upregulated GPX4 and SLC7A11, indicating an inhibitory effect on ferroptosis. WB results showed that SIRT1 expression was enhanced in the DSS + NaB group. In addition, immunofluorescence staining demonstrated that compared with the DSS group, GPX4 expression was increased in macrophages in the DSS + NaB group. Conclusions: NaB alleviates IBD by modulating SIRT1-associated signaling molecules and inhibiting ferroptosis, including inhibiting macrophage ferroptosis.
Chen et al. (2026) studied this question.