Ricerc@Sapienza

Probiotics are emerging as a very fascinating therapeutic strategy for inflammatory bowel diseases (IBD). Their ability to recondition the altered microbiota of IBD patients could be enriched by selective delivery of bioactive molecules directly in the intestine via genetically engineered probiotics. Palmitoylethanolamide (PEA) is an endogenous ALIAmide that exhibits a wide range of anti-inflammatory and anti-angiogenic effects associated with the ability to restore the intestinal permeability in impaired epithelial barrier conditions. Thus, PEA takes place as a very promising candidate to reverse the pathological course of the disease in IBD patients. Because of PEA's unpredictable concentrations after oral administration, the present research plan is aimed at evaluating the effects of genetically modified bacteria able to biosynthesize PEA in an acute colitis model in mice. We will test the probiotic Lactobacillus paracasei subsp paracasei F19 (LP), that we have already engineered with human NAPEpld gene (pNAPE-LP) (European Patent EP3040070A1, Inventors: Augusto Sannetti, Rosario Cuomo, Giovanni Sarnelli, Giuseppe Esposito), in a set of in-vitro and in-vivo experiments to evaluate his ability (i) to release PEA under the boost of an ultra-low dose of exogenous palmitate and (ii) lead to a colitis resolution in comparison with LP transformed by the empty plasmid vector (pLP). Also, we will assess the efficacy of pNAPE-LP/palmitate formulation in cultured human colonic biopsies deriving from ulcerative colitis patients.