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.

驴乳溶菌酶（DML）是炎症性肠病（IBD）的潜在治疗剂，但其机理仍不清楚。在这里，我们报道了DML改善了结肠炎小鼠的体重减轻，结肠损伤和粘膜炎症。此外，DML增加了咬合和小带咬合蛋白1的表达，并减少了claudin-2的表达，从而改善了机械屏障功能。它还抑制肿瘤坏死因子-α和白介素-13的表达，并降低髓过氧化物酶水平，以增强免疫屏障功能。DML增加了肠道微生物群组成的多样性，促进了益生菌的生长并抑制了有害细菌，这表明DML在微生物屏障功能中发挥了重要作用。确定了DML的X射线结构，其中包含具有保守活性位点的核心结构。结合亚位点的不同构象和残基可能表明与底物的结合能力不同。这些结果表明，口服DML是治疗IBD的有前途的新疗法。