Donkey milk lysozyme ameliorates dextran sulfate sodium-induced colitis by improving intestinal barrier function and gut microbiota composition

Abstract

Donkey milk lysozyme (DML) is a potential therapeutic agent for inflammatory bowel disease (IBD), while the mechanism remains obscure. Here, we reported that DML ameliorated weight loss, colon damage and mucosal inflammation in colitis mice. Additionally, DML increased the expression of occluding and zonula occludens-1, and reduced that of claudin-2, thus improving mechanical barrier function. It also inhibited the expression of tumour necrosis factor-α and interleukin-13, and reduced the myeloperoxidase level for strengthen of immune barrier function. DML increased gut microbiota composition diversity, promoting growth of probiotics and inhibiting pernicious bacteria, indicating that DML played an important role in microbial barrier function. The X-ray structure of DML was determined, which contained a core structure with conserved active site. The different conformation and residues of binding subsites may indicate diverse binding ability to substrates. These results suggested that oral administration of DML is a promising novel therapeutic for treatment of IBD.

Keywords

• Donkey milk lysozyme
• Colitis
• Dextran sulfate sodium
• Intestinal barrier function
• Gut microbiota composition
• Crystal structure