Abstract: The antimicrobial peptide β-defensin also has an immunomodulatory effect. It plays an important role in maintaining intestinal homeostasis. This study aimed to investigate the role of mouse β-defensin 14 (mBD14) in inflammatory bowel disease (IBD). Lactiplantibacillus plantarum was used as a carrier for targeted delivery of mBD14 into the mouse intestine by genetic engineering technology. Meanwhile, the effect of the bacterium on acute colitis induced by dextran sulfate sodium (DSS) in mice was assessed. The results showed that mBD14-expressing Lactiplantibacillus plantarum alleviated the symptoms of colitis. Moreover, the bacterium modulated the gut microbiota, protected intestinal barrier function, attenuated the expression of pro-inflammatory cytokines and inhibited the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) and downstream inflammatory pathways. Thus, the current study reveals a protective effect of mBD14-expressing Lactiplantibacillus plantarum against DSS-induced colitis, which provides a rationale for the development of prophylactic strategies based on probiotics and antimicrobial peptides for the prevention of IBD.

Key words: antimicrobial peptides; inflammatory bowel disease; mouse β-defensin 14; Lactiplantibacillus plantarum; intestinal homeostasis