CRAMP-encoding Lactobacillus plantarum FCQHC24 attenuates experimental colitis in mice

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.

Automated summary

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.