Mechanistically, the treatment downregulated ACSL4 expression, inhibited JAK2/STAT3 phosphorylation, and upregulated the expression of GPX4, Occludin, and Claudin-1.<h4>Conclusion</h4>The combination of Ononin and <i>Lactobacillus paracasei</i> effectively ameliorated DSS-induced colitis in mice. The gene discussed is ACSL4; the disease is colitis.