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Oral Delivery of Mouse β-Defensin 14 (mBD14)-Producing Lactococcus lactis NZ9000 Attenuates Experimental Colitis in
Haizhi Tian1,2, Jiahong Li1,2, Xiaopei Chen1,2
1State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214126, China.
Abstract:
Antimicrobial peptides (AMPs) play essential roles in maintaining intestinal health and have been suggested as possible therapeutic strategies against inflammatory bowel disease (IBD). However, the instability of AMPs in the process of transmission in vivo limits their application in the treatment of IBD. In this study, we constructed the mBD14-producing Lactococcus lactis NZ9000 (L. lactis/mBD14) to achieve enteric delivery of mBD14 and evaluated its protective effect on dextran sodium sulfate (DSS)-induced colitis. Mice treated with L. lactis/mBD14 exhibited milder symptoms of colitis (P < 0.01). Additionally, L. lactis/mBD14 treatment reversed DSS-induced epithelial dysfunction and reduced the production of pro-inflammatory cytokines in colon (P < 0.01). Mechanistically, L. lactis/mBD14 significantly inhibited NOD-like receptor pyrin domain containing three inflammasome-mediated pro-inflammatory response (P < 0.05) and regulated microbiota homeostasis by promoting the abundance of probiotic bacteria Akkermansia muciniphila and Faecalibacterium prausnitzii and decreasing the pathogenic Escherichia coli (P < 0.01). Taken together, this study demonstrates the protective effect of L. lactis/mBD14 in DSS-induced colitis, and suggests that oral administration of L. lactis/mBD14 may represent a potential therapeutic strategy for IBD.
Insights
Engineered Lactococcus lactis delivers antimicrobial peptide mBD14 to treat inflammatory bowel disease (IBD). This probiotic approach reduced colitis symptoms and inflammation in mice, offering a promising therapeutic strategy for IBD.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Antimicrobial peptides (AMPs) are crucial for gut health and potential treatments for inflammatory bowel disease (IBD).
- In vivo instability of AMPs hinders their therapeutic application for IBD.
- Developing stable delivery systems for AMPs is essential for effective IBD treatment.
Purpose of the Study:
- To engineer Lactococcus lactis to produce and deliver the antimicrobial peptide mBD14 for treating dextran sodium sulfate (DSS)-induced colitis.
- To evaluate the therapeutic efficacy of L. lactis/mBD14 in a mouse model of IBD.
- To elucidate the underlying mechanisms of L. lactis/mBD14 in mitigating colitis.
Main Methods:
- Construction of mBD14-producing Lactococcus lactis NZ9000 (L. lactis/mBD14) for enteric delivery.
- Induction of colitis in mice using dextran sodium sulfate (DSS).
- Administration of L. lactis/mBD14 to DSS-treated mice and assessment of colitis severity, epithelial function, cytokine production, inflammasome activity, and gut microbiota composition.
Main Results:
- L. lactis/mBD14 treatment significantly alleviated DSS-induced colitis symptoms and reversed epithelial dysfunction (P < 0.01).
- Treatment reduced pro-inflammatory cytokine production and inhibited the NLRP3 inflammasome-mediated inflammatory response (P < 0.01, P < 0.05).
- L. lactis/mBD14 modulated gut microbiota homeostasis, increasing beneficial bacteria (Akkermansia muciniphila, Faecalibacterium prausnitzii) and decreasing pathogenic Escherichia coli (P < 0.01).
Conclusions:
- Engineered L. lactis/mBD14 demonstrates significant protective effects against DSS-induced colitis in mice.
- Oral administration of L. lactis/mBD14 represents a potential therapeutic strategy for inflammatory bowel disease.
- This approach enhances AMP delivery, restores gut barrier function, and modulates the gut microbiome.
