4.7 Article

CRAMP-encoding Lactobacillus plantarum FCQHC24 attenuates experimental colitis in mice

Journal

FOOD BIOSCIENCE
Volume 42, Issue -, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.fbio.2021.101111

Keywords

Colitis; Cathelicidin-related antimicrobial peptide; Lactobacillus plantarum; Engineered probiotics

Funding

  1. National Natural Science Foundation of China [80270666, 81870439, 81973322, 81901517]
  2. Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province [BK20200026]
  3. Jiangsu Province Recruitment Plan for High-level, Innovative and Entrepreneurial Talents (Innovative Research Team)
  4. Collaborative Innovation Center of Food Safety and Quality Control of Jiangsu Province
  5. Fundamental Research Funds for the Central Universities [JUSRP221037, JUSRP22007]
  6. National First-Class Discipline Program of Food Science and Technology [JUFSTR20180103]
  7. Wuxi Social Development Funds for Interna-tional Science & Technology Cooperation [WX0303B010518180007PB]
  8. Jiangsu Province Qing Lan Project
  9. Jiangsu Province Six Summit Talents Program [YY-038]
  10. Wuxi Establishment Site for Key Medical disciplines [ZDXK012]
  11. Young Project of the Wuxi Health and Family Planning Commission [Q201815]

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In this study, engineered probiotics encoding CRAMP were shown to increase colonic CRAMP production, reduce colon shortening and weight loss, and suppress inflammatory responses in experimental colitis. These findings suggest that CRAMP-encoding L. plantarum may have therapeutic potential for colitis through modulation of colonic CRAMP production.
Cathelicidin-related antimicrobial peptide (CRAMP) has been reported to have positive immune-modulatory and anti-inflammatory effects. However, the effect of recombinant CRAMP-encoding Lactobacillus plantarum on experimental colitis is unknown. In this study, 4 strains of CRAMP-encoding L. plantarum FCQHC24 were constructed using genetic engineering. They were administered orally to mice for 4 consecutive days after experimental colitis was induced using 3% dextran sodium sulfate (DSS). Disease severity was determined. The levels of colonic inflammatory cytokines and CRAMP and activation of transcription factor nuclear factor-kappa B (NF-kappa B) were analyzed. The 4 engineered CRAMP-encoding L. plantarum strains significantly increased the colonic CRAMP production, especially the strains containing the Usp45 signal peptide, accompanied by reduced colon shortening and body weight (bw) loss. In addition, treatment with the engineered probiotics decreased the levels of colonic pro-inflammatory cytokines (IL-6, IL-1 beta and TNF-alpha) and increased the level of colonic anti-inflammatory cytokine IL-10 in DSS-induced experimental colitis. The engineered probiotics suppressed DSS-induced phosphorylation and activation of colonic p38, extracellular signal-regulated kinase 1/2, and NF-kappa B. Taken together, this study showed that CRAMP-encoding L. plantarum FCQHC24 had the therapeutic potential for colitis by modulating colonic CRAMP production.

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