Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice

Area of Science:

• Gastroenterology
• Microbiology
• Immunology

Background:

• Palmitoylethanolamide (PEA), an endogenous N-acylethanolamide, shows therapeutic potential for ulcerative colitis (UC).
• High doses of PEA are required in vivo, limiting its clinical application.
• Current research focuses on novel delivery methods for PEA.

Purpose of the Study:

• To develop a novel method for enhanced in situ intestinal delivery of PEA.
• To investigate the therapeutic efficacy of a genetically engineered probiotic, pNAPE-LP, in a murine model of UC.

Main Methods:

• Engineered Lactobacillus paracasei F19 (pNAPE-LP) to express NAPE-PLD for PEA production.
• Administered pNAPE-LP with ultra-low palmitate supply to a mouse model of UC.
• Assessed clinical and histological scores, neutrophil infiltration, inflammatory markers, and epithelial barrier integrity.

Main Results:

• Co-administration of pNAPE-LP and palmitate led to time-dependent PEA release.
• Significant amelioration of clinical and histological damage scores observed.
• Reduced neutrophil infiltration, pro-inflammatory cytokines, and oxidative stress markers.
• Markedly improved epithelial barrier integrity.

Conclusions:

• pNAPE-LP with ultra-low palmitate supply represents a novel strategy for in situ intestinal PEA delivery.
• This approach effectively controls intestinal inflammation in inflammatory bowel disease.
• Offers a promising therapeutic avenue for managing UC.