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Volume 22
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Article

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

by
Giuseppe Esposito
1,2,
Marcella Pesce
3,
Luisa Seguella
1,
Jie Lu
4,
Chiara Corpetti
1,
Alessandro Del Re
1,
Fatima Domenica Elisa De Palma
5,
Giovanni Esposito
6,
Walter Sanseverino
2 and
Giovanni Sarnelli
1,2,7,*
1
Department of Physiology and Pharmacology “V. Erspamer”, Sapienza University of Rome, 00185 Rome, Italy
2
Nextbiomics S.R.L., 80100 Naples, Italy
3
Department of Clinical Medicine and Surgery, University of Naples “Federico II”, 80131 Naples, Italy
4
Department of Anatomy and Cell Biology, China Medical University, Shenyang City, Liaoning 110122, China
5
CEINGE-Biotecnologie Avanzate s.c.a r.l., Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, 80131 Naples, Italy
6
Department of Advanced Biomedical Sciences, University of Naples Federico II, 80131 Naples, Italy
7
UNESCO Chair Staff Member, University of Naples “Federico II”, 80100 Naples, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(6), 2945; https://doi.org/10.3390/ijms22062945
Submission received: 8 February 2021 / Revised: 11 March 2021 / Accepted: 11 March 2021 / Published: 14 March 2021
(This article belongs to the Special Issue The Role of Microbiota in Wellness and Target Therapy: Molecular and Mechanistic Insights)
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Abstract

Palmitoylethanolamide (PEA) is an N-acylethanolamide produced on-demand by the enzyme N-acylphosphatidylethanolamine-preferring phospholipase D (NAPE-PLD). Being a key member of the larger family of bioactive autacoid local injury antagonist amides (ALIAmides), PEA significantly improves the clinical and histopathological stigmata in models of ulcerative colitis (UC). Despite its safety profile, high PEA doses are required in vivo to exert its therapeutic activity; therefore, PEA has been tested only in animals or human biopsy samples, to date. To overcome these limitations, we developed an NAPE-PLD-expressing Lactobacillus paracasei F19 (pNAPE-LP), able to produce PEA under the boost of ultra-low palmitate supply, and investigated its therapeutic potential in a murine model of UC. The coadministration of pNAPE-LP and palmitate led to a time-dependent release of PEA, resulting in a significant amelioration of the clinical and histological damage score, with a significantly reduced neutrophil infiltration, lower expression and release of pro-inflammatory cytokines and oxidative stress markers, and a markedly improved epithelial barrier integrity. We concluded that pNAPE-LP with ultra-low palmitate supply stands as a new method to increase the in situ intestinal delivery of PEA and as a new therapeutic able of controlling intestinal inflammation in inflammatory bowel disease.
Keywords: inflammatory bowel disease; palmitoylethanolamide; ulcerative colitis; probiotic; Lactobacillus paracasei; pharmacotherapy inflammatory bowel disease; palmitoylethanolamide; ulcerative colitis; probiotic; Lactobacillus paracasei; pharmacotherapy

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MDPI and ACS Style

Esposito, G.; Pesce, M.; Seguella, L.; Lu, J.; Corpetti, C.; Del Re, A.; De Palma, F.D.E.; Esposito, G.; Sanseverino, W.; Sarnelli, G. Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice. Int. J. Mol. Sci. 2021, 22, 2945. https://doi.org/10.3390/ijms22062945

AMA Style

Esposito G, Pesce M, Seguella L, Lu J, Corpetti C, Del Re A, De Palma FDE, Esposito G, Sanseverino W, Sarnelli G. Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice. International Journal of Molecular Sciences. 2021; 22(6):2945. https://doi.org/10.3390/ijms22062945

Chicago/Turabian Style

Esposito, Giuseppe, Marcella Pesce, Luisa Seguella, Jie Lu, Chiara Corpetti, Alessandro Del Re, Fatima Domenica Elisa De Palma, Giovanni Esposito, Walter Sanseverino, and Giovanni Sarnelli. 2021. "Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice" International Journal of Molecular Sciences 22, no. 6: 2945. https://doi.org/10.3390/ijms22062945

APA Style

Esposito, G., Pesce, M., Seguella, L., Lu, J., Corpetti, C., Del Re, A., De Palma, F. D. E., Esposito, G., Sanseverino, W., & Sarnelli, G. (2021). Engineered Lactobacillus paracasei Producing Palmitoylethanolamide (PEA) Prevents Colitis in Mice. International Journal of Molecular Sciences, 22(6), 2945. https://doi.org/10.3390/ijms22062945

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