<i>Human Lysozyme</i> Transgenic Maize Improves Colonic Inflammation by Inhibiting the cGAS/STING Signaling Pathway in DSS‐Induced Colitis Mice

ABSTRACT Inflammatory bowel disease (IBD) is a refractory condition caused by autoimmune disorders. The recurrent nature and poor prognosis of this disease necessitate long‐term treatment, substantially increasing the financial burden on patients. Human lysozyme (HLZ) possesses the function of ameliorating intestinal inflammation. Meanwhile, maize is the world's most popular food crop, valued for its easy cultivation and low cost. In this study, the HLZ gene was introduced into maize. HLZ transgenic maize showed specific high accumulation of HLZ in kernels with no negative effect on maize yield, protein content and protein quality. Moreover, the total protein extracted from the transgenic endosperm exhibited strong lysozyme activity (291.15 U/mg). Using a dextran sulfate sodium (DSS)‐induced colitis mouse model, we observed that HLZ transgenic maize restored colon length and intestinal barrier function in mice. The results of further molecular analyses indicated that HLZ transgenic maize inhibited intestinal epithelial cell apoptosis and altered the intestinal microbiota. Furthermore, HLZ transgenic maize inhibited the cGAS/STING signaling pathway by ameliorating DSS‐induced mitochondrial dysfunction. In addition, the results of transcriptomic sequencing revealed that HLZ transgenic maize reversed DSS‐induced alterations in the expression of genes related to colonic inflammation (e.g., IFN‐β and IL6 ). This research deepened the understanding of the functional mechanisms for HLZ in improving intestinal immune system. Our results indicate that HLZ transgenic maize provides an effective and low‐cost approach for clinically ameliorating IBD symptoms. As a food resource, HLZ transgenic maize might benefit a wider range of people than drugs.