Human Gut Microbiota and Their Production of Endocannabinoid-like Mediators Are Directly Affected by a Dietary Oil

Dietary omega-3 polyunsaturated fatty acids (-3 PUFAs) and the gut microbiome affect each other. We investigated the impact of supplementation with oil (BO), rich in stearidonic acid (SDA), on the human gut microbiome. Employing the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), we simulated the ileal and ascending colon microbiomes of four donors. Our results reveal two distinct microbiota clusters influenced by BO, exhibiting shared and contrasting shifts. Notably, and abundance underwent similar changes in both clusters, accompanied by increased propionate production in the colon. However, in the ileum, cluster 2 displayed a higher metabolic activity in terms of BO-induced propionate levels. Accordingly, a triad of bacterial members involved in propionate production through the succinate pathway, namely , was identified particularly in this cluster, which also showed a surge of second-generation probiotics, such as , in the colon. Finally, we describe for the first time the capability of gut bacteria to produce -acyl-ethanolamines, and particularly the SDA-derived -stearidonoyl-ethanolamine, following BO supplementation, which also stimulated the production of another bioactive endocannabinoid-like molecule, commendamide, in both cases with variations across individuals. Spearman correlations enabled the identification of bacterial genera potentially involved in endocannabinoid-like molecule production, such as, in agreement with previous reports, in the case of commendamide. This study suggests that the potential health benefits on the human microbiome of certain dietary oils may be amenable to stratified nutrition strategies and extend beyond -3 PUFAs to include microbiota-derived endocannabinoid-like mediators.