Oleoylethanolamide treatment affects gut microbiota composition and the expression of intestinal cytokines in Peyer’s Patches of mice

The lipid sensor oleoylethanolamide (OEA), an endogenous high-a nity agonist of peroxisome proliferator-activated receptor-α (PPAR-α) secreted in the proximal intestine, is endowed with several distinctive homeostatic properties, such as control of appetite, anti-in ammatory activity, stimulation of lipolysis and fatty acid oxidation. When administered exogenously, OEA has bene cial e ects in several cognitive paradigms; therefore, in all respects, OEA can be considered a hormone of the gut- brain axis. Here we report an unexplored modulatory e ect of OEA on the intestinal microbiota and on immune response. Our study shows for the rst time that sub-chronic OEA administration to mice fed a normal chow pellet diet, changes the faecal microbiota pro le, shifting the Firmicutes:Bacteroidetes ratio in favour of Bacteroidetes (in particular Bacteroides genus) and decreasing Firmicutes (Lactobacillus), and reduces intestinal cytokines expression by immune cells isolated from Peyer’s patches. Our results suggest that sub-chronic OEA treatment modulates gut microbiota composition towards a “lean-like phenotype”, and polarises gut-speci c immune responses mimicking the e ect of a diet low in fat and high in polysaccharides content.