Human Gut Microbes Produce EPA- and DHA-Derived Oxylipins, but not N-Acyl-Ethanolamines, From Fish Oil

We recently reported that human fecal microbiota colonized in a simulator of the human intestinal microbiome ecosystem (SHIME) process dietary oil from Buglossoides arvensis (Ahiflower), rich in the n-3 polyunsaturated fatty acid (PUFA) stearidonic acid, to the endocannabinoid (eCB)-like N-stearidonoyl-ethanolamine. Here, we assess if human fecal microbiota collected in summer and winter and inoculated in the SHIME (simulating four different intestinal sections; ileum, and ascending, transverse and descending colon) and then treated with fish oil (FO) rich in triglyceride-esterified docosahexaenoic and eicosapentaenoic acids (DHA and EPA, respectively) result in the formation of the corresponding anti-inflammatory and anticancer n-3 PUFA metabolites, including N-acylethanolamines and oxylipins. Effluents were collected every day and analyzed by LC-MS/MS for PUFA metabolites and bacterial and short-chain fatty acids (SCFA) composition during an initial 7-day treatment with vehicle and then a further 7-day treatment with FO (DHA and EPA in equal amounts, 910 mg/day each). A time-dependent increase of DHA and EPA was observed, particularly with the summer microbiota in all intestinal sections except for the duodenum, which does not contain gut microbiota. The formation of 17-hydroxy-docosahexaenoic acid from DHA, and 15-hydroxy- and 18-hydroxy-eicosapentaenoic acid from EPA was observed within the summer samples. However, no accumulation of N-docosahexaenoyl-ethanolamine or N-eicosapentaenoyl-ethanolamine, nor any other N-acyl-ethanolamines, was detected in any intestinal section and season. These data suggest that a human fecal microbiome cultivated in a SHIME processes DHA and EPA-containing triglycerides to oxylipins with known activity on the host, but not necessarily to N-acyl-ethanolamines.